Windable bone implant for encapsulating bone material

Abstract

A bone implant (10) for encapsulating bone material (12) is provided. The bone implant includes a cover (18), which may be a biodegradable mesh. The cover is configured to be wound to a certain diameter to at least partially encapsulate the bone material within the cover. In some embodiments, the cover includes a body portion (80) and a closure portion (82) adjacent to the body portion. The closure portion is configured to hold the cover in its wound configuration to a predetermined diameter to at least partially encapsulate the bone material. A kit and method of using the bone implant are also provided.

Description

Background Technology

[0001] The use of bone grafts and bone replacement materials in orthopedic medicine is well-known. While bone trauma can regenerate without forming scar tissue, fractures and other orthopedic injuries take a long time to heal, during which time the bone cannot independently support physiological loads. Metal pins, screws, rods, plates, and meshes are often needed to replace the mechanical function of injured bone. However, metal is significantly harder than bone. The use of metal implants can lead to a decrease in bone density around the implantation site due to stress shielding. Physiological stress and corrosion can cause metal implants to fracture. Unlike bone, which can remodel and heal small injuries and cracks to prevent larger damage and failure, damaged metal implants can only be replaced or removed. The body's natural cellular healing and remodeling mechanisms coordinate the removal of bone and bone grafts by osteoclasts and the formation of bone by osteoblasts.

[0002] Conventionally, bone regeneration is achieved by filling the bone repair site with a bone graft (e.g., bone material). Over time, the bone graft integrates with the host, and new bone remodels the graft. For placement of bone grafts, monolithic pre-formed bone grafts or bone implants containing granular bone formed within a carrier are typically used. Generally, whether monolithic or granular and formed within a carrier, the resulting implant is substantially solid at implantation and therefore does not conform to the implantation site. The implant is also substantially intact at implantation and therefore offers limited customization options, such as by adding autologous grafts or altering the implant's shape.

[0003] The use of bone grafts is often limited by the available shape and size of the graft. Bone grafts are often available pre-shaped and pre-sized. However, many surgeons prefer to utilize local bone obtained during surgery by combining it with another graft, which cannot be done if the graft is pre-shaped or pre-sized. Patient autografts can be combined with moldable grafts, but these moldable grafts may not be included and may migrate from the wound site. Furthermore, bone grafts using cortical bone remodel slowly due to their limited porosity. Traditional bone substitutes remodel faster but do not provide immediate mechanical support. In addition, while bone substitutes can be used to fill oddly shaped bone defects, such materials are less suitable for wrapping bone or repairing bone surfaces.

[0004] Therefore, it would be beneficial to provide bone implants that are filled with available bone materials (e.g., natural and / or synthetic bone particles), can be easily sized in length and diameter, or can otherwise be adjusted at the point of care for implantation at a variety of surgical sites. Bone implants that can be customized in real time according to the size and shape of bone defects in the patient's anatomy and the type of bone material to be used would also be desirable. Kits and methods related to filling and implanting these adjustable bone implants would also be desirable. Summary of the Invention

[0005] Bone implants are available that can partially or completely encapsulate bone material and can be easily sealed and implanted at the surgical site. These implants can be customized to suit the size and shape of the bone defect and the type of bone material to be used. Kits and methods related to filling and implanting these implants are also provided.

[0006] In one embodiment, a bone implant for encapsulating bone material is provided. The bone implant includes a cover, which in some aspects is a biodegradable mesh. The cover is configured to be wound to a certain diameter to at least partially encapsulate the bone material within the cover.

[0007] In another embodiment, the bone implant for encapsulating bone material includes a cover, wherein the cover includes a main portion and a closure portion adjacent to the main portion. In some embodiments, the closure portion is configured to hold the cover in a coiled configuration to a predetermined diameter to at least partially encapsulate the bone material.

[0008] In one embodiment, a kit for manufacturing a bone implant is provided. The kit includes a bone implant, which may be a cover. In many aspects, the cover is configured to be wound to a certain diameter to at least partially encapsulate bone material within the cover. The kit may also include at least one of: (i) a plurality of size adjustment rings or cylinders configured to engage the bone implant to adjust the implant to a desired diameter; or (ii) a funnel having a variable diameter, said funnel being configured to load the cover with a certain amount of said bone material. In some embodiments, the kit may also include a desiccant to prevent hydrolytic degradation during storage.

[0009] In another embodiment, the kit for manufacturing a bone implant includes: a cover, wherein the cover includes a main portion and a closure portion adjacent to the main portion, the closure portion being configured to hold the cover in a coiled configuration to a predetermined diameter to at least partially encapsulate bone material; and an adhesive.

[0010] In one embodiment, a method for implanting a bone implant at a surgical site is provided. The method includes: providing a bone implant including a cover configured to be wound to a diameter to at least partially enclose bone material within the cover; enclosing the bone material within the cover by adapting the cover to a wound configuration; and placing the bone implant at the surgical site to implant the bone implant at the surgical site.

[0011] In another embodiment, a method of implanting a bone implant at a surgical site includes: providing a bone implant comprising a cover, the cover comprising a main portion and a closed portion adjacent to the main portion, the closed portion being configured to hold the cover in a coiled configuration to a predetermined diameter to at least partially encapsulate bone material; encapsulating the bone material in the cover by adapting the cover to a coiled configuration; and placing the bone implant at the surgical site to implant the bone implant at the surgical site.

[0012] While several embodiments have been disclosed, other embodiments of this application will become apparent to those skilled in the art from the following detailed description, taken in conjunction with the accompanying drawings. It will be apparent to them that modifications are possible in various obvious respects, all without departing from the spirit and scope of this disclosure. Therefore, the detailed description is to be regarded as substantially illustrative rather than restrictive. Attached Figure Description

[0013] This disclosure will become more apparent from the detailed description following the accompanying drawings.

[0014] Figure 1 A perspective view of a bone implant used to encapsulate bone material is shown. The bone implant includes a cover, which is a mesh configured to be wound to a certain diameter to encapsulate the bone material within the cover. The bone material is secured within the wound mesh by strands of thread that act as closure members and are tied around the wound mesh.

[0015] Figure 2 It shows the relationship with Figure 1 A perspective view of a bone implant similar to the one used to encapsulate bone material. The bone material is secured by a wound mesh, which is sealed with adhesive at the opposite ends and / or along the length of the wound mesh at the overlaps.

[0016] Figure 3 It shows the relationship with Figure 2 A perspective view of a bone implant similar to the one used to encapsulate bone material, wherein the bone material is secured by a coiled mesh that is sealed at opposite ends with sutures (not shown).

[0017] Figure 4A A schematic diagram of a flat cover for encapsulating bone implant material is shown. The cover has a predetermined length and width and multiple strands attached at predetermined intervals to one edge of the cover. Once the cover is rolled around the bone material or graft, the strands can be used to secure the bone material by tying the strands around the rolled cover. The diagram shows multiple strands spaced apart from each other along the edge of the cover.

[0018] Figure 4B It shows the relationship with Figure 4A The diagram illustrates a similar flat cover for encapsulating bone implants. The cover in this diagram has different pre-selected lengths and multiple strands attached at predetermined intervals to one edge of the cover's length. Once the cover is rolled around the bone material or graft, the strands can be used to secure the bone material by tying the strands around the rolled cover.

[0019] Figure 5A A perspective view of a cover in a coiled configuration is shown, shaped as a tube without bone material. The strands around the tube are open.

[0020] Figure 5B It shows the coiled configuration Figure 5A A perspective view of the covering, in which strands of thread are tied around the rolled-up covering.

[0021] Figure 6 A schematic diagram of a flat covering is shown, which has strands along its width for securing bone material. The exterior of the covering has visual markers at predefined intervals to help the user resize the covering, thus forming a rolled-up covering of a specific diameter.

[0022] Figure 7A A perspective view of a mesh in a flat configuration is shown, with bone material on the inner surface of the mesh.

[0023] Figure 7B It shows the coiled configuration Figure 7A A perspective view of a mesh in which bone material is encapsulated within the mesh.

[0024] Figure 7C The partially wound configuration is shown. Figure 7A A perspective view of a mesh in which bone material is partially enclosed in a partially wound mesh.

[0025] Figure 7DA schematic diagram shows a covering (e.g., a mesh) of encapsulating bone material wound into a large-diameter tubular structure. In this embodiment, the diameter of the tube can be reduced by applying opposing tensile forces, as indicated by the arrows, at the open ends.

[0026] Figure 7E A schematic diagram shows a covering formed by winding encapsulating bone material into a small-diameter tubular structure. The diameter of the tube is reduced by applying opposing tensile forces, as indicated by the arrows in 7D.

[0027] Figure 8A , Figure 8B and Figure 8C Different sizes of size adjustment rings are shown. These size adjustment rings are used to control the diameter of the cover as the selected ring slides over the outer surface of the rolled cover, so as to allow the cover to have a uniform diameter and size.

[0028] Figure 9A A perspective view of a size-adjustable cylinder that can be used to fill a covering and control the diameter of the covering is shown.

[0029] Figure 9B The illustration shows rolled covers of different sizes to be filled with bone material using funnels of different sizes.

[0030] Figure 10 A perspective view of a variable-diameter funnel that can be used to fill bone implants (e.g., coverings) is shown.

[0031] Figure 11 A perspective view of a tray is shown, which includes a bone implant containing encapsulated bone material secured with a closure member, which is a strand of thread knotted together to hold a covering (e.g., a net) in a wound position and to encapsulate the bone material within the covering.

[0032] Figure 12 A schematic diagram of a flat cover for encapsulating bone implants is shown. The cover includes a main body portion with narrower inter-line spacing and a closed portion with wider inter-line spacing.

[0033] Figure 13A It is used in Figure 12 This diagram illustrates the use of inelastic lines in the main body and / or closed portion of the covering. Inelastic lines typically have a narrower spacing between them.

[0034] Figure 13B It is used in Figure 12 This diagram illustrates the use of inelastic lines in the closed portion of the covering. The inelastic lines are arranged in a sinusoidal pattern to impart structural flexibility. These lines typically have a wider spacing than the main body.

[0035] Figure 14A A schematic diagram of a flat cover for securing bone material is shown. The cover (e.g., a mesh) has visual markers spaced apart from each other at predefined intervals inside to help the user resize the cover, thus forming a rolled cover with a specific diameter, length, and width. The cover may have adhesive at discrete areas. Here, the adhesive is shown as a strip on the right side of the flat cover, which holds the cover in a rolled configuration and at least partially encapsulates the loaded bone material within the cover.

[0036] Figure 14B It is in a coiled configuration Figure 14A The diagram shows a perspective view of the covering, in which the adhesive holds the covering in a rolled configuration.

[0037] It should be understood that the accompanying drawings are not drawn to scale. Furthermore, the relationships between objects in the drawings may not be to scale, and in fact, they may have inverse relationships regarding size. The drawings are intended to aid in understanding and clarifying the structure of each object shown, and therefore, some features may be exaggerated to illustrate specific structural characteristics. Detailed Implementation

[0038] definition

[0039] For the purposes of this specification and the appended claims, unless otherwise indicated, all figures expressing the amount of an ingredient, percentage or proportion of material, reaction conditions, and other numerical values ​​used in this specification and the claims shall be understood to be modified in all cases by the term “about.” Similarly, when a value is expressed as an approximation by using the antecedent “about,” it shall be understood that the value forms another embodiment of the stated value by + / - 10%. Therefore, unless indicated to the contrary, the numerical parameters set forth in the following specification and the appended claims are approximations that may vary depending on the desired characteristics sought to be obtained through this disclosure. To a minimum, and without attempting to limit the application of the equivalence principle to the scope of the claims, each numerical parameter shall be interpreted at least according to the number of significant digits reported and by applying general rounding techniques. Moreover, as used in the specification and including the appended claims, the singular forms “a,” “an,” and “the” include the plural, and unless the context clearly indicates otherwise, references to a particular numerical value include at least that particular value. A range may be expressed herein as “about” or “approximately” to a particular value and / or “about” or “approximately” to another particular value. When expressing such a range, another embodiment includes from one particular value and / or to another particular value.

[0040] While the numerical ranges and parameters used to illustrate the broad scope of this application are approximations, the numerical values ​​described in specific examples are reported as precisely as possible. However, any numerical value inherently contains some error that is necessarily caused by the standard deviation found in its corresponding test measurement. Furthermore, all ranges disclosed herein should be understood to encompass any and all subranges contained therein. For example, the range “1 to 10” includes any and all subranges between (and including) the minimum value of 1 and the maximum value of 10, i.e., any and all subranges having a minimum value equal to or greater than 1 and a maximum value equal to or less than 10, such as 5.5 to 10.

[0041] As used herein, bioactive agents, bioactive compounds, or bioactive materials may be used interchangeably to refer to compounds or entities that alter, inhibit, activate, or otherwise affect biological or chemical events. For example, bioactive agents may include, but are not limited to, bone-forming or chondrogenic proteins or peptides, anti-AIDS substances, anticancer substances, antibiotics, immunosuppressants, antiviral substances, enzyme inhibitors, hormones, neurotoxins, opioids, hypnotics, antihistamines, lubricants, sedatives, anticonvulsants, muscle relaxants and anti-Parkinson's substances, anticonvulsants and muscle contractile agents (including channel blockers), miotics and anticholinergics, antiglaucoma compounds, antiparasitic and / or antiprotozoal compounds, modulators of cell-extracellular matrix interactions (including cell growth inhibitors and antiadhesion molecules), vasodilators, inhibitors of DNA, RNA or protein synthesis, antihypertensive drugs, analgesics, antipyretics, steroidal and nonsteroidal anti-inflammatory agents, anti-angiogenic factors, angiogenic factors, antisecretory factors, anticoagulants and / or antithrombotic agents, local anesthetics, ophthalmic drops, prostaglandins, antidepressants, antipsychotic substances, antiemetics, and imaging agents. In some embodiments, the bioactive agent is a drug. The bioactive agent further comprises RNA, such as siRNA, and osteoclast-stimulating factors. In some embodiments, the bioactive agent may be a factor that stops, removes, or reduces the activity of bone growth inhibitors. In some embodiments, the bioactive agent is a growth factor, cytokine, extracellular matrix molecule, or fragment or derivative thereof, such as a cell attachment sequence, such as RGD. In some embodiments, the bioactive agent includes nutrients, including but not limited to vitamin A, vitamin D, vitamin E, vitamin K2, isoflavones, milk proteins, caffeine, sugars, or combinations thereof.

[0042] As used in this article, biocompatibility is defined to describe materials that do not induce undesirable long-term effects when administered in vivo.

[0043] As used in this article, bone refers to cortical bone, cancellous bone, or cortical-cancellous bone of autologous, allogeneic, xenogeneic, or transgenic origin.

[0044] As used herein, bone graft means any implant prepared according to the embodiments described herein, and may therefore include expressions such as bone material and periosteum.

[0045] Bone materials include demineralized bone. As used herein, demineralized material refers to any material produced by removing mineral material from tissue, such as bone tissue. In some embodiments, demineralized bone material may be added to a bone void filler. Demineralized bone materials described herein include formulations containing less than 5% by weight, 4% by weight, 3% by weight, 2% by weight, or 1% by weight of calcium. Partially demineralized bone (e.g., formulations having more than 5% by weight of calcium but containing less than 100% of the original starting amount of calcium) is also considered to be within the scope of this disclosure. In some embodiments, partially demineralized bone formulations containing more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the original starting amount of calcium. In some embodiments, the demineralized bone has less than 95% of its original mineral content. In some embodiments, the demineralized bone has less than 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, or 5% of its original mineral content. Demineralization is intended to encompass expressions such as “substantially demineralized,” “partially demineralized,” “shallowly demineralized,” and “completely demineralized.” In some embodiments, part or all of the surface of the bone may be demineralized. For example, part or all of the surface of the bone material may be demineralized to a depth of about 100 micrometers to about 5000 micrometers, or about 150 micrometers to about 1000 micrometers.In some embodiments, part or all of the surface of the bone material may be demineralized to approximately 100 micrometers, 150 micrometers, 200 micrometers, 250 micrometers, 300 micrometers, 350 micrometers, 400 micrometers, 450 micrometers, 500 micrometers, 550 micrometers, 600 micrometers, 650 micrometers, 700 micrometers, 750 micrometers, 800 micrometers, 850 micrometers, 900 micrometers, 950 micrometers, 1000 micrometers, 1050 micrometers, 1100 micrometers, 1150 micrometers, 1200 micrometers, and 1250 micrometers. Meter, 1300 micrometers, 1350 micrometers, 1400 micrometers, 1450 micrometers, 1500 micrometers, 1550 micrometers, 1600 micrometers, 1650 micrometers, 1700 micrometers, 1750 micrometers, 1800 micrometers, 1850 micrometers, 1900 micrometers, 1950 micrometers, 2000 micrometers, 2050 micrometers, 2100 micrometers, 2150 micrometers, 2200 micrometers, 2250 micrometers, 2300 micrometers, 2350 micrometers, 2400 micrometers, 2450 micrometers, 2500 micrometers 2550 micrometers, 2600 micrometers, 2650 micrometers, 2700 micrometers, 2750 micrometers, 2800 micrometers, 2850 micrometers, 2900 micrometers, 2950 micrometers, 3000 micrometers, 3050 micrometers, 3100 micrometers, 3150 micrometers, 3200 micrometers, 3250 micrometers, 3300 micrometers, 3350 micrometers, 3400 micrometers, 3450 micrometers, 3500 micrometers, 3550 micrometers, 3600 micrometers, 3650 micrometers, 3700 micrometers, 3750 micrometers, 38 Depths ranging from 0.00 micrometers, 3850 micrometers, 3900 micrometers, 3950 micrometers, 4000 micrometers, 4050 micrometers, 4100 micrometers, 4150 micrometers, 4200 micrometers, 4250 micrometers, 4300 micrometers, 4350 micrometers, 4400 micrometers, 4450 micrometers, 4500 micrometers, 4550 micrometers, 4600 micrometers, 4650 micrometers, 4700 micrometers, 4750 micrometers, 4800 micrometers, 4850 micrometers, 4900 micrometers, 4950 micrometers to approximately 5000 micrometers. Depending on requirements, bone materials may include demineralized materials.

[0046] Partially demineralized bone refers to a formulation with a calcium content greater than 5% by weight but less than 100% of the original starting amount. In some embodiments, partially demineralized bone comprises 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 5 ... 2%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, and / or 99% of the original starting amount of calcium.

[0047] In some embodiments, the demineralized bone can be approximately 1% to 99% surface demineralized. In some embodiments, the demineralized bone is 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50%. 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, and / or 99% surface demineralization. In various embodiments, the demineralized bone can be about 15-25% surface demineralized. In some implementations, the demineralized bone is surface demineralized at 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, and / or 25%.

[0048] As used herein, demineralized bone matrix (DBM) refers to any material produced by removing minerals from bone tissue. In some embodiments, the DBM composition used herein comprises a formulation containing less than 5% calcium, and in some embodiments, less than 1% by weight of calcium. In some embodiments, the DBM composition comprises a formulation containing less than 5% by weight, 4% by weight, 3% by weight, 2% by weight, and / or 1% by weight of calcium. In other embodiments, the DBM composition comprises partially demineralized bone (e.g., a formulation having more than 5% by weight of calcium but containing less than 100% of the original starting amount of calcium).

[0049] As used in this article, osteoinductive properties refer to the ability of a substance to act as a template or material along which bone can grow.

[0050] As used in this article, osteogenic material refers to material containing living cells capable of differentiating into osteogenic tissue.

[0051] As used herein, osteoinductive properties refer to the ability to recruit cells from the host that have the potential to stimulate new bone formation. Any material that can induce the formation of ectopic bone in animal soft tissue is considered osteoinductive. For example, most osteoinductive materials induce bone formation in athymic rats when measured according to the following method: Edwards et al., “Osteoinduction of Human Demineralized Bone: Characterization in a Rat Model,” Clinical Orthopaedics & Res., 357:219-228, December 1998, which is incorporated herein by reference.

[0052] As used herein, surface demineralization refers to bone-derived elements having at least about 90% by weight of their original inorganic mineral content. In some embodiments, surface demineralization contains at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, and / or 99% by weight of their original inorganic material. As used herein, "fully demineralized" means bone containing less than 8% of its original mineral content. In some embodiments, fully demineralized bone contains about 8%, 7%, 6%, 5%, 4%, 3%, 2%, and / or 1% of its original mineral content.

[0053] The expression "average length to average thickness ratio" used for DBM fibers in this application refers to the ratio of the longest average dimension (average length) of the fiber to its shortest average dimension (average thickness). This is also known as the fiber's "aspect ratio".

[0054] As used herein, fibrous refers to bone elements with a fiber length-to-thickness ratio or aspect ratio of about 50:1 to about 1000:1. In some embodiments, the fiber length-to-thickness ratio or aspect ratio is about 50:1, 75:1, 100:1, 125:1, 150:1, 175:1, 200:1, 225:1, 250:1, 275:1, 300:1, 325:1, 350:1, 375:1, 400:1, 425:1, 450:1, 475... The ratios are 1, 500:1, 525:1, 550:1, 575:1, 600:1, 625:1, 650:1, 675:1, 700:1, 725:1, 750:1, 775:1, 800:1, 825:1, 850:1, 875:1, 900:1, 925:1, 950:1, 975:1, and / or 1000:1. In their overall appearance, fibrous bone elements can be described as bone fibers, lines, strips, or sheets. Typically, when producing sheets, their edges tend to curl towards each other. The appearance of fibrous bone elements can be substantially linear, or they can be coiled like a spring. In some embodiments, bone fibers have irregular shapes, including, for example, linear, serpentine, or curved shapes. Bone fibers are demineralized; however, some of the original mineral content may be retained when required by a particular embodiment. In various embodiments, bone fibers are mineralized. In some implementations, the fiber is a combination of demineralization and mineralization.

[0055] As used herein, non-fibrous refers to elements whose average width is substantially greater than the average thickness of fibrous bone elements or whose aspect ratio is less than about 50:1 to about 1000:1. Non-fibrous bone elements are shaped in a substantially regular manner or in a specific configuration, such as triangular prisms, spheres, cubes, cylinders, and other regular shapes. In contrast, particles such as fragments, debris, or powder have irregular or random geometries. It should be understood that some dimensional variations may occur during the manufacture of the elements in this application, and elements exhibiting such dimensional variations are within the scope of this application and are intended to be understood herein as being within the boundaries established by the expressions “substantially irregular” and “substantially regular.”

[0056] As used herein, a rolled-up covering refers to a covering (e.g., a net) that is rolled up by rotating or turning along its length or width until it is in a cylindrical or substantially cylindrical shape.

[0057] The term "at least partially encapsulated" means that the covering partially encapsulates the bone material. In some embodiments, the covering will have open ends to partially encapsulate the bone material. These ends may be sutured, sealed, or otherwise closed.

[0058] Bone implants, devices, kits, and methods can be used to treat spinal conditions such as, for example, degenerative disc disease, herniated discs, osteoporosis, anterior vertebral displacement, stenosis, scoliosis and other curvature abnormalities, kyphosis, tumors, and fractures. Bone implants, devices, kits, and methods can be used in other skeletal and bone-related applications, including those associated with diagnosis and treatment. They can also be used as an alternative to surgical treatment in which the patient is in a prone or supine position, and / or with various surgical approaches to the spine and other body areas, including anterior, dorsal, midline dorsal, lateral, posterior, and / or anterior approaches. Bone implants, devices, kits, and methods can also be used alternatively with surgeries for the treatment of the lumbar, cervical, thoracic, sacral, and pelvic regions of the spine. They can also be used on animals, bone models, and other inanimate objects, for example, in training, testing, and validation.

[0059] In various embodiments, the bone implant includes a biodegradable mesh comprising poly(lactide-co-glycolic acid) (PLGA), polylactide (PLA), polyglycolic acid (PGA), D-lactide, D,L-lactide, L-lactide, D,L-lactide-co-ε-caprolactone, D,L-lactide-co-glycolic acid-co-ε-caprolactone, L-lactide-co-ε-caprolactone, or combinations thereof. In some embodiments, the mesh comprises bone material, such as, for example, hydroxyapatite, calcium phosphate, ceramic, or combinations thereof. The bone material, such as hydroxyapatite, calcium phosphate, ceramic, or combinations thereof, may be part of the threads or yarns of the covering, or may be loaded into the covering in granular form and then encapsulated by the covering.

[0060] Bone implants

[0061] refer to Figures 1 to 3 , Figure 4A , Figure 4B , Figure 5A , Figure 5B and Figure 6 A bone implant 10 is provided, which is customizable and configured to encapsulate bone material 12. Bone material 12 can be completely or at least partially encapsulated by a covering 18. The bone implant is configured to be cut and shaped to any size and diameter required for a specific surgical site to match the patient's anatomy. Therefore, the customizable covering can be used in a wide variety of spinal fusion surgeries and other applications.

[0062] Bone implants are constructed for applications such as minimally invasive midline lumbar fusion, posterior cervical fusion, and oral and maxillofacial reconstruction. They can also be used to heal vertebral compression fractures, interbody fusion, other minimally invasive procedures, posterolateral fusion, correction of scoliosis in adults or children, treatment of long bone defects, osteochondral defects, ridge enlargement (teeth / craniofacial, e.g., patients with missing teeth), sublaminal trauma, tibial plateau defects, filling bone cysts, wound healing, peri-traumatic healing, shaping (cosmetic / plastic / reconstructive surgery), and other uses.

[0063] The covering 18 is biodegradable and is configured to be wound into a generally tubular structure having a diameter D for at least partially encasing the bone material 12. It should be understood that the covering may also be made of a non-biodegradable material, or may be made of both a biodegradable and a non-biodegradable material.

[0064] The covering 18 defines a generally flat surface 19 having a first edge 14, a second edge 16, a third edge 20, and a fourth edge 22. The first edge 14 is positioned opposite the second edge 16, and the third edge 20 is positioned opposite the fourth edge 22. In some aspects, the surface 19 is constructed as a square or rectangle, which can be rolled into different or variable widths W, different or variable lengths L, or different or variable diameters, such as... Figure 4A , Figure 4B and Figure 6 As shown. In this way, implants can be customized to meet bone defects of different sizes.

[0065] The first edge 14 includes at least one closure member 24 configured to hold the cover 18 in a coiled configuration having a predetermined diameter D for at least partially enclosing the bone material 12. In some aspects, the third edge 20 and the fourth edge 22 may be sealed by a practicing clinician, for example, when used at a surgical site, by sutures, adhesives, or other equivalent methods.

[0066] In various embodiments, the cover 18 includes a mesh 32, which is substantially composed of mesh, or is composed of mesh. The mesh 32 has an inner surface 34 and an outer surface 36, such as... Figure 5A and Figure 5B As shown. As further described in this disclosure, both the length and width of the mesh can be adjusted by trimming it to any desired size before winding it to completely or partially encapsulate the bone material. Therefore, the wound mesh of this application can be customized to match the patient's anatomy as needed at the surgical site.

[0067] The inner or outer surface may include a plurality of spaced-apart internal markings 38 (not shown) or external markings 40, which are configured to help adjust the size of the covering 18 or the mesh 32. The markings 38 may be a mesh of different colored threads, or other visual indicators, such as notches, knots, raised areas, etc. For example, in Figure 6 In the process, marking 40 includes lines of different colors extending longitudinally at different lengths along the length of the covering 18 to help the surgeon or another clinician readjust the size of the mesh to form the desired winding product of a specific diameter. Fluorescent surgical dyes and / or coloring additives approved for medical devices may be used. For example, useful dyes include, but are not limited to, D&C Blue 6, D&C Blue 9, D&C Green 5, [phthalocyanine (2-)]copper, FD&C Blue 2, chromium-cobalt-aluminum oxide, ferric ammonium citrate, pyrogallol, or hematoxylin and eosin.

[0068] In various embodiments, the cover 18 may have different lengths and widths. In some embodiments, the width of the cover 18 defines the circumference of the rolled-up cover and can vary from about 10 mm to about 100 mm, more specifically from about 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, 25 mm, 26 mm, 27 mm, 28 mm, 29 mm, 30 mm, 31 mm, 32 mm, 33 mm, 34 mm, 35 mm, 36 mm, 37 mm, 38 mm, 39 mm, 40 mm, 41 mm, 42 mm, 43 mm, 44 mm, 45 mm, 46 mm, 47 mm, 48 mm, 49 mm, 50 mm, etc. m, 51mm, 52mm, 53mm, 54mm, 55mm, 56mm, 57mm, 58mm, 59mm, 60mm, 61mm, 62mm, 63mm, 64mm, 65mm, 66mm, 67mm, 68mm, 69mm, 70mm, 71mm, 72mm, 73mm, 74mm, 75mm, 7 6mm, 77mm, 78mm, 79mm, 80mm, 81mm, 82mm, 83mm, 84mm, 85mm, 86mm, 87mm, 88mm, 89mm, 90mm, 91mm, 92mm, 93mm, 94mm, 95mm, 96mm, 97mm, 98mm, 99mm changes to about 100mm. In some embodiments, the rolled-up covering may have a length ranging from about 2 cm, 4 cm, 6 cm, 8 cm, 10 cm, 12 cm, 14 cm, 16 cm, 18 cm, 20 cm, 22 cm, and 24 cm. In one embodiment, the length of the rolled-up covering may vary from about 4 cm to about 14 cm.

[0069] The diameter of the rolled covering can range from approximately 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, 21mm, 22mm, 23mm, 24mm, 25mm, 26mm, 27mm, 28mm, 29mm, 30mm, 31mm, 32mm, 33mm, 34mm, 35mm, 36mm, 37mm, 38mm, 39mm, 40mm, 41mm, 42mm, 43mm, 44mm, 45mm, 46mm, 47mm, 48mm, 49mm, 50mm, 51mm. The diameter of the rolled-up cover can vary from approximately 7 mm to approximately 25 mm, ranging from approximately 100 mm. (The numbers 52 mm, 53 mm, 54 mm, 55 mm, 56 mm, 57 mm, 58 mm, 59 mm, 60 mm, 61 mm, 62 mm, 63 mm, 64 mm, 65 mm, 66 mm, 67 mm, 68 mm, 69 mm, 70 mm, 71 mm, 72 mm, 73 mm, 74 mm, 75 mm, 76 mm, 77 mm, 78 mm, 79 mm, 80 mm, 81 mm, 82 mm, 83 mm, 84 mm, 85 mm, 86 mm, 87 mm, 88 mm, 89 mm, 90 mm, 91 mm, 92 mm, 93 mm, 94 mm, 95 mm, 96 mm, 97 mm, 98 mm, and 99 mm.)

[0070] exist Figure 6 In the illustrated embodiment, markings 40 are positioned at specific lengths along the length of the covering, such as 22mm, 38mm, 53mm, 69mm, and 88mm, which allows the surgeon to trim the covering to these dimensions.

[0071] like Figure 4A , Figure 4B and Figure 6 As shown, at least one closure member 24 may be positioned on a first edge 14 or a third edge 20 of the cover 18. In other embodiments, the closure member may be positioned on a second edge 16 and / or a fourth edge 22. Whether the closure member is attached to or detached from the cover, its function is to hold the cover 18 in a coiled configuration for at least partially enclosing the bone material 12. Similarly, as... Figure 4A , Figure 4B and Figure 6 As shown, the closure member 24 may include one or more strands 42 configured to be tied, consisting essentially of strands, or composed of strands. The strands 42 may be positioned at various distances along the length or width of any of the edges of the cover 18.

[0072] In some embodiments, the strands are positioned on the edge of the cover 18 opposite the winding edge. For example, in one aspect, winding the cover around the second edge 16 would require at least one closure member 24 positioned around the first edge 14. In some implementations, the strands 42 can be spaced at predetermined intervals, ranging from approximately 0.5cm, 0.6cm, 0.7cm, 0.8cm, 0.9cm, 1.0cm, 1.2cm, 1.4cm, 1.5cm, 1.6cm, 1.7cm, 1.8cm, 1.9cm, 2.0cm, 2.2cm, 2.3cm, 2.4cm, 2.5cm, 2.6cm, 2.7cm, 2.8cm, 2.9cm, 3.0cm, 3.1cm, 3.2cm, 3.3cm, 3.4cm, 3.5cm, 3.6cm, 3.7cm, 3.8cm, 3.9cm, 4.0cm, 4.1cm, 4.2cm, 4.4cm, 4.5cm, 4.6cm, 4.7cm, 4.8cm, 4.9cm, 5.0cm, 5.1cm, ... The lengths range from 5.2cm, 5.2cm, 5.3cm, 5.5cm, 5.6cm, 5.7cm, 5.8cm, 5.9cm, 6.0cm, 6.1cm, 6.2cm, 6.3cm, 6.4cm, 6.5cm, 6.6cm, 6.7cm, 6.8cm, 6.9cm, 7cm, 7.1cm, 7.2cm, 7.3cm, 7.4cm, 7.5cm, 7.6cm, 7.7cm, 7.8cm, 7.9cm, 8cm, 8.1cm, 8.2cm, 8.3cm, 8.4cm, 8.5cm, 8.6cm, 8.7cm, 8.8cm, 8.9cm, 9cm, 9.1cm, 9.2cm, 9.3cm, 9.4cm, 9.5cm, 9.6cm, 9.7cm, 9.8cm, and 9.9cm to approximately 10cm. Therefore, the mesh 32 includes its own self-closing strands 42, which secure bone material within the coiled mesh, which can be customized to any desired combination of width, length, and / or diameter. By providing an adjustable mesh with built-in self-closing and / or self-sealing features, bone material can be completely contained and will not migrate from the surgical site. In this way, the mesh 32 enables clinicians to provide coiled mesh filled with any desired type and volume of bone material.

[0073] exist Figure 5A The image shows a wound net 32, in which V-shaped strands 42 are in an untied structural type. Figure 5B In the middle, strand 42 is tied around the coiled net 32. Similarly, Figure 1 The diagram shows the closure member 24 knotted around the cover 18 to secure the bone material within the rolled-up cover.

[0074] The strands can be formed from the same material as the web or a different material, and can be interwoven or integrated into the fabric of the web. The strands can be manufactured via coating, 3D printing, and / or screen printing. In some embodiments, the strands are made of non-absorbable filaments, nylon, cable nylon, polyester, and polypropylene. In other embodiments, the strands are biodegradable and reabsorbable, and can be made of polyglycolic acid (PGA), rapid polyglycolic acid (RPGA), polydioxanone (PDO), and polycaprolactone or polyglycolic acid-co-caprolactone (PGCL). In some embodiments, the strands can be made of hydroxyapatite, calcium phosphate, ceramics, or combinations thereof.

[0075] In various embodiments, the strands can have lengths ranging from approximately 5cm, 6cm, 7cm, 8cm, 9cm, 10cm, 11cm, 12cm, 13cm, 14cm, 15cm, 16cm, 17cm, 18cm, 19cm, 20cm, 21cm, 22cm, 23cm, 24cm, 25cm, 26cm, 27cm, 28cm, 29cm, 30cm, and 31cm to approximately 32cm. In many embodiments, the diameter of each strand can vary depending on its material. For example, in some aspects, for non-absorbable strands, the diameter of each strand can vary from approximately 0.01mm, 0.02mm, 0.03mm, 0.04mm, 0.05mm, 0.06mm, 0.07mm, 0.08mm, 0.09mm, 0.1mm, 0.15mm, 0.2mm, 0.3mm, 0.35mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm to approximately 0.9mm. In some aspects, for reabsorbable strands, the diameter of each strand can vary from approximately 0.02 mm, 0.03 mm, 0.04 mm, 0.05 mm, 0.06 mm, 0.07 mm, 0.08 mm, 0.09 mm, 0.1 mm, 0.15 mm, 0.2 mm, 0.3 mm, 0.35 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm to approximately 0.9 mm.

[0076] To assist surgeons or clinicians in readjusting the size of the covering at the surgical site, strands 42 are positioned along any of the edges of the covering 18 and may also be different colors to indicate the length along the dimensions of the covering. The dyes used for the strands of the covering can be those suitable for use with... Figure 6 The same kind of dye is used to color other markings or visual indicators present on the covering 18.

[0077] In various implementation schemes, the covering may have, for example: Figures 7A to 7E Many configurations are shown. For example, in Figure 7A In the middle, the cover 18 has a planar or unwound configuration; in Figure 7B In the middle, the covering 18 is in a rolled-up configuration; and in Figure 7C In the middle, the covering is rolled up in 18 parts. Figure 7D and Figure 7E In the middle, the covering 18 is a tubular structure with different diameters.

[0078] In some embodiments, when in a wound configuration, the cover 18 has opposite open ends 60 and 62, which are configured to be pulled in opposite directions along axis AA to reduce the diameter of the cover, thereby at least partially encapsulating the bone material within the cover, such as... Figure 7D As shown. In these implementations, clinicians may begin by rolling the covering into a tubular shape with a large diameter, loading the bone graft onto it, and then as... Figure 7D As shown, pulling along the long axis AA causes the covering to collapse around the encapsulated bone graft.

[0079] In some implementations, the tubular covering is configured by using different diameters (e.g., d1, d2, d3, etc.). Figure 8A , Figure 8B and Figure 8C The size adjustment ring 44 (as shown) is used to adjust to different diameters. In other embodiments, such as Figure 9AAs shown, instead of pulling along the long axis AA to cause the rolled-up covering to collapse around the bone material, clinicians can use cylinders 46 of different diameters to compress the bone material within the tubular covering to a controlled diameter. The ring and size-adjustable cylinder are available in sizes from approximately 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, 21mm, 22mm, 23mm, 24mm, 25mm, 26mm, 27mm, 28mm, 29mm, 30mm, 31mm, 32mm, 33mm, 34mm, 35mm, 36mm, 37mm, 38mm, 39mm, 40mm, 41mm, 42mm, 43mm, 44mm, 45mm, 46mm, 47mm, 48mm, 49mm, 50mm, and 51mm. The diameter varies from m, 52mm, 53mm, 54mm, 55mm, 56mm, 57mm, 58mm, 59mm, 60mm, 61mm, 62mm, 63mm, 64mm, 65mm, 66mm, 67mm, 68mm, 69mm, 70mm, 71mm, 72mm, 73mm, 74mm, 75mm, 76mm, 77mm, 78mm, 79mm, 80mm, 81mm, 82mm, 83mm, 84mm, 85mm, 86mm, 87mm, 88mm, 89mm, 90mm, 91mm, 92mm, 93mm, 94mm, 95mm, 96mm, 97mm, 98mm, 99mm to approximately 100mm.

[0080] In other implementations, such as Figure 9B As shown, clinicians can start with a small-diameter covering, but increase the diameter by adding excessive bone material. In these implementations, such as... Figure 9BAs shown, funnels 48 of different diameters are used to load the covering material with bone. The funnels can have sizes ranging from approximately 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, 21mm, 22mm, 23mm, 24mm, 25mm, 26mm, 27mm, 28mm, 29mm, 30mm, 31mm, 32mm, 33mm, 34mm, 35mm, 36mm, 37mm, 38mm, 39mm, 40mm, 41mm, 42mm, 43mm, 44mm, 45mm, 46mm, 47mm, 48mm, 49mm, 50mm, and 51mm. Diameters ranging from 52mm, 53mm, 54mm, 55mm, 56mm, 57mm, 58mm, 59mm, 60mm, 61mm, 62mm, 63mm, 64mm, 65mm, 66mm, 67mm, 68mm, 69mm, 70mm, 71mm, 72mm, 73mm, 74mm, 75mm, 76mm, 77mm, 78mm, 79mm, 80mm, 81mm, 82mm, 83mm, 84mm, 85mm, 86mm, 87mm, 88mm, 89mm, 90mm, 91mm, 92mm, 93mm, 94mm, 95mm, 96mm, 97mm, 98mm, and 99mm to approximately 100mm are available. Clinicians can use methods such as... Figure 10 The variable diameter funnel 50 shown is loaded with a rolled-up covering to achieve a similar result.

[0081] like Figure 12 As shown, the cover 18 of the bone implant 10 may include a main body portion 80 and a closure portion 82 adjacent to the main body portion. As in other embodiments described in this application, Figure 12 The covering shown can be a biodegradable mesh. By controlling the spacing of the lines in the main body and the closed portion, the porosity of the covering (e.g., the mesh) can be controlled, and thus the inflow and outflow of cells and other materials that allow bone growth can be controlled.

[0082] The mechanical properties of the covering can be altered by changing the pattern of the threads in the woven net. For example, the main body 80 of the covering 18 may include, be substantially composed of, or be composed of a configuration similar to that of a fishing net, wherein the net threads 84 are in a narrower pattern (e.g., as shown in the image). Figure 12 The yarns are woven in a roughly rectangular pattern (as shown). These yarns are narrowly spaced apart. In the narrower pattern of the body portion 80, the yarns 84 are woven more tightly to produce a web with a smaller porosity. In some embodiments, the aperture of the body portion can be, for example, from about 100 μm to about 200 μm.

[0083] The closed portion 82 may include a wider pattern (e.g., as shown in the image). Figure 12 The closure portion 82 has a generally rhomboid woven mesh 86, which is substantially composed of or consists of these meshes. These meshes are spaced further apart than the main body portion. The mesh 86 of the closure portion 82 is woven more loosely to create a mesh with greater porosity. In some embodiments, the aperture can be, for example, from about 0.1 mm to about 2 mm. In some embodiments, the aperture of the closure portion 82 varies from about 0.1 mm to about 5 mm, from about 0.5 mm to about 3 mm, or from about 1 mm to about 2 mm. The closure portion will be more flexible, and when the covering is wound, the closure portion can wrap around the main body portion with narrower weave threads, and then the main body portion can be positioned within the separate wider threads of the closure portion to at least partially encapsulate the bone material within the covering.

[0084] In some implementations, 3D printing can be used to provide covers having threads woven in different geometric patterns to achieve different mechanical properties at different locations on the cover. Three-dimensional (3D) printing is an additive printing process used to manufacture three-dimensional solid objects from digital models. 3D printing technologies are considered additive processes because they involve applying successive layers of material to create the printed object. Conventional 3D printing allows objects to be produced by depositing material one layer at a time on a flat manufacturing platform. Once the first layer is deposited, a second layer is deposited on top of the first layer. This process is repeated as necessary to produce multi-layered solid objects. Recently, computer-implemented apparatuses and methods for producing covers (e.g., meshes) for bone implants have become available, as described in US 10064726 and US 10442175, which are incorporated herein by reference as fully illustrated herein. Therefore, conventional weaving, knitting, injection molding, or computer-generated 3D printing methods can be used to produce a cover 18 that has one geometry for the lines of the main body and a different geometry for the lines of the closed portion; however, in both cases, a cover with a continuous surface is produced.

[0085] In various embodiments, the main body portion 80 and the closing portion 82 are arranged adjacent to each other as a continuous cover or net with location-specific mechanical properties. In some aspects, the main body portion 80 comprises a net woven from inelastic, non-stretchable threads 88, which may be porous or non-porous, such as... Figure 13AAs shown. The closure portion 82 is more flexible, comprising a mesh made of inelastic, non-stretchable threads 90, printed in a sinusoidal pattern to give the closure portion 82 structural elasticity (stretchability), and can be wound around the body portion to hold the covering in the wound configuration to a predetermined diameter to at least partially enclose the bone material, such as... Figure 13B As shown. In some embodiments, the closure portion 82 includes multiple highly porosity layers that can be wrapped around the body portion 80. In some embodiments, the closure portion 82 can be stretched and wound around the body portion 80 without adding any large amount of additional polymer web or significantly reducing the porosity of the body. In some embodiments, the closure portion is (i) more flexible than the body portion or (ii) more deformable than the body portion.

[0086] In some embodiments, the bone material may comprise hydroxyapatite, calcium phosphate, and / or ceramic (e.g., 90-95% hydroxyapatite). The bone material (e.g., hydroxyapatite, calcium phosphate, and / or ceramic) may be formed as one or more threads or yarns of a covering (e.g., a mesh). In some embodiments, the bone material (e.g., hydroxyapatite, calcium phosphate, and / or ceramic) may be combined with a polymer and form one or more threads or yarns of the covering. For example, the threads or yarns of the covering may be made of a hyperelastic bone material. This may be part of the body portion and / or the closure portion of the covering.

[0087] In some embodiments, the cover 18 is prepared by 3D printing, and in some aspects, the ink used in the printing process may be inherently viscous. Once wound, the resulting cover can remain partially or completely wound due to the viscous nature of its material, such as... Figure 7B and Figure 7C As shown. In other embodiments, suitable materials include natural materials, synthetic polymeric reabsorbable materials, synthetic polymeric non-reabsorbable materials, and other materials. Natural web materials include filaments, extracellular matrix (such as DBM, collagen, ligaments, tendon tissue, or others), filament-elastin, elastin, collagen, and cellulose. Synthetic polymeric reabsorbable materials include poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-glycolic acid) (PLGA), poly(p-dioxanone), PVA, polyurethane, polycarbonate, etc.

[0088] In some embodiments, the body portion 80 may be prepared from a first set of threads 84, and the closed portion 82 may be prepared from a second set of threads 86. Threads 84 and 86 may be prepared from the same or different materials. However, in some aspects, the threads of the covering may be woven in different ways to achieve different mechanical properties. In some embodiments, the print head of the 3D printing apparatus may be configured to extrude more than one type of material for printing the covering 18. In other embodiments, the 3D printing apparatus may have a first print head configured to extrude a first material to form threads 84 and a second print head configured to extrude a second material to form threads 86. Suitable materials for preparing the covering 18 include natural materials, synthetic polymeric reabsorbable materials, synthetic polymeric non-reabsorbable materials, and other materials. Natural web materials include filaments, extracellular matrix (such as DBM, collagen, ligaments, tendon tissue, or others), filament-elastin, elastin, collagen, and cellulose. Synthetic polymer reabsorbable materials include poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-glycolic acid) (PLGA), poly(p-dioxanone), PVA, polyurethane, polycarbonate, etc.

[0089] In some implementations, whether or not 3D printed, the covering 18 or the mesh 32 may be made of shape-memory polymers and / or alloys to allow the mesh to move from a planar configuration to a wound configuration to at least partially encapsulate the bone material, without the need for locking or tying mechanisms, such as Figure 7B and Figure 7C As shown. In other embodiments, the mesh may be designed to include hooks for adhesion to specific portions of the mesh. For example, in some aspects, hooks can be 3D printed by layer deposition of flowable ink onto the printed surface of the mesh, wherein specific portions contain voids into which the ink can flow and solidify. When the 3D printed mesh is removed from the printed surface, the mesh retains positive protrusions that match the voids. These protrusions function like hooks and can interact with the mesh to allow the mesh to adhere itself in a coiled configuration. In one embodiment, the first mating surface of the mesh includes protrusions or hooks ( Figure 14A 31) and the second mating surface includes a matching gap ( Figure 14B 35), used to maintain the web in a wound configuration. In another embodiment, refer to Figure 4B The cover 18 may have hooks or other protrusions (not shown) on the first edge 14 as a substitute for the strands 42. The opposite second edge 16 may have matching gaps (not shown) to keep the web in a wound configuration.

[0090] Other embodiments of the cover as described in this disclosure Figure 14AThis is a schematic diagram of a flat covering used to fix bone material, wherein the covering (e.g., a mesh) has multiple spaced visual markers 40 inside to aid in adjusting the size of the covering. The markers 40 are positioned at predefined intervals to help the user readjust the size of the covering, thereby forming a coiled covering of a specific diameter. The markers 40 can be lines of different colors, or other visual indicators, such as notches, knots, protrusions, etc. The lines of different colors can extend longitudinally or laterally and can be used to indicate different sizes to help the surgeon readjust the size of the mesh, thereby producing a coiled mesh with a specific diameter, length, and width.

[0091] In other respects, network 32 includes internal 34 (such as...) Figure 14A (as shown) and external 36 (as shown) Figure 14B (As shown). In some aspects, all or a portion of the interior and / or exterior of the net comprises an adhesive material disposed thereon. In other embodiments, the net comprises an interior and an exterior, a portion of which has mating surfaces configured to hold the net in a winding configuration.

[0092] In some implementations, adhesives can be used to hold the web in a wound configuration. Figure 14A In one embodiment, the net 32 ​​has an adhesive 92, shown as a strip, on the right side of the interior 34 of the flat cover, the adhesive being configured such that the net 32... Figure 14B As shown, after being wound, it is attached to the outer surface 36 of the mesh (in Figure 14B (As shown in the diagram). Adhesive 92 may have a release layer 93, which can be removed before, during, or after winding to expose the adhesive.

[0093] In some embodiments, the adhesive may be applied at discrete areas of the cover or throughout the entire interior and / or exterior of the cover. In some embodiments, the adhesive may be added to the cover before, during, or after it is wound to the desired diameter, length, and / or width.

[0094] In various embodiments, the adhesive material is (i) water-activated; (ii) the adhesive material is applied upon use; and (iii) the adhesive material contains a volatile solvent that makes the mesh sticky upon evaporation to provide self-adhesion. When the adhesive material is applied upon use, the adhesive may be provided in a separate container (e.g., a bottle) and applied, for example, by adding adhesive thread after winding the mesh to encapsulate the bone material.

[0095] In various embodiments, suitable adhesive materials for closing the net into a wound or partially wound configuration may include, for example, cyanoacrylates (such as B Braun's tissue adhesive (histoacryl), which is n-butyl-2-cyanoacrylate; or Dermasbond, which is 2-octylcyanoacrylate); epoxy compounds, dental resin sealants, dental resin adhesives, glass ionomer adhesives, polymethyl methacrylate, gelatin-resorcinol-formaldehyde glue, collagen-based glue, inorganic binders such as zinc phosphate, magnesium phosphate or other phosphate-based adhesives, zinc carboxylate, L-DOPA (3,4-dihydroxy-L-phenylalanine), proteins, carbohydrates, glycoproteins, mucopolysaccharides, other polysaccharides, hydrogels, protein-based binders such as fibrin glue and mussel-derived adhesive proteins, and any other suitable substances. The adhesives may be selected based on their bonding time; for example, in some cases, temporary adhesives may be required, such as for fixation during and after surgical procedures for a limited time, while in other cases, permanent adhesives may be required. In some implementations, bone implants can be sealed by applying a volatile or water-soluble solvent to the mesh material. This solvent temporarily softens the mesh or causes its surface to dissolve, allowing the mesh to bond and adhere to adjacent meshes. Once the volatile or water-soluble solvent is removed from the application site, the mesh will harden or settle, thus forming an adhesive between the two parts of the mesh at the site of solvent application. In cases where the mesh is made of a reabsorbable material, an adhesive that maintains adhesion while the material is present in the body can be selected.

[0096] net

[0097] In various embodiments, the covering 18 is an adjustable, biodegradable mesh. The mesh may be made of woven threads configured to allow inward cell growth while retaining bone material within the compartments of the bone implant. The threads of the mesh may have a predetermined thickness of about 0.01 mm to about 2.0 mm, about 0.05 mm to about 1.0 mm, or about 0.1 mm to about 0.5 mm. The thickness of the threads may be uniform along the length of each thread or vary across the length of each thread. In some embodiments, some threads have a greater thickness than others. The dimensions of the threads can be set to allow for customizable apertures between the threads. In some embodiments, the bone implant is configured to facilitate the transfer of material and / or other material around the surgical site. After implantation at the surgical site, the bone implant may engage, control, or otherwise modulate, or may allow surrounding material such as cells or tissue to penetrate the mesh.

[0098] The net is constructed to be wound into a certain diameter, such as Figure 1 , Figure 2 , Figure 3 , Figure 5A , Figure 5B, Figure 7D , Figure 7E and Figure 14B As shown. The mesh is a fully customizable mesh that can be adjusted in both length and diameter to fit the needs of a specific patient's anatomy. For example, the mesh may include diameter sizes between about 1 mm and about 100 mm. In some embodiments, the mesh includes diameters of about 2 mm, 5 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm, 35 mm, 40 mm, 45 mm, 50 mm, 55 mm, 60 mm, 65 mm, 70 mm, 75 mm, 80 mm, 85 mm, 90 mm, 95 mm, or 100 mm. In some embodiments, the mesh includes a length or width between about 0.1 cm and about 24 cm. In some implementations, the net includes a length or width of approximately 0.1cm, 0.2cm, 0.3cm, 0.35cm, 0.4cm, 0.5cm, 0.6cm, 0.7cm, 0.8cm, 0.9cm, 1cm, 2cm, 3cm, 4cm, 5cm, 6cm, 7cm, 8cm, 9cm, 10cm, 11cm, 12cm, 13cm, 14cm, 15cm, 16cm, 17cm, 18cm, 19cm, 20cm, 21cm, 22cm, 23cm, or 24cm.

[0099] The network can be porous, allowing for fluid transfer and cell infiltration, enabling osteoblasts to create bone grafts. For example, in... Figure 6In the diagram, mesh 32 shows pores at locations 33A and 33B as an exploded view. In many embodiments, the mesh is porous to allow cell inflow and outflow when the bone material is completely encapsulated by the mesh. To optimize cell or fluid migration through the mesh, the pore size can be optimized for the viscosity and surface tension of the fluid or the size of the cells. Porous meshes can have pore sizes ranging from about 1 micrometer to about 2000 micrometers, from about 1 micrometer to about 1500 micrometers, from about 1 micrometer to about 1000 micrometers, from about 1 micrometer to about 500 micrometers, from about 1 micrometer to about 250 micrometers, from about 100 micrometers to about 2000 micrometers, from about 150 micrometers to about 1500 micrometers, from about 200 micrometers to about 1000 micrometers, and from about 250 micrometers to about 500 micrometers. In some implementations, the pore size can be approximately 1 micrometer, 10 micrometers, 20 micrometers, 50 micrometers, 80 micrometers, 100 micrometers, 120 micrometers, 150 micrometers, 180 micrometers, 200 micrometers, 220 micrometers, 250 micrometers, 280 micrometers, 300 micrometers, 350 micrometers, 400 micrometers, 450 micrometers, 500 micrometers, 550 micrometers, 600 micrometers, 650 micrometers, 700 micrometers, 750 micrometers, 800 micrometers, 850 micrometers, 900 micrometers, 950 micrometers, 1000 micrometers, 1250 micrometers, 1450 micrometers, 1650 micrometers, 1850 micrometers, 2000 micrometers, 2100 micrometers, 2200 micrometers, 2300 micrometers, 2400 micrometers, 2500 micrometers, or 2600 micrometers. Generally, the pore size of the mesh should be small enough to retain bone material and prevent it from falling through the mesh.

[0100] The mesh may have varying degrees of permeability on its surface. It can be permeable, semi-permeable, or impermeable. Permeability can be related to cells, fluids, proteins, growth factors, bone morphogenetic proteins, or others. In other embodiments, the material may be woven.

[0101] The mesh can have any suitable custom configuration. Among the various configurations, the mesh can be customized into tubular structures of various diameters and lengths that can be easily fitted into the patient's anatomy.

[0102] Furthermore, in some embodiments, the flexibility of the wound net allows it to be manipulated into multiple compartments. For example, in a tubular embodiment, the tube can be formed into multiple compartments by tying strands around the tube at one or more points, or by other suitable mechanisms such as coiling, twisting, knotting, stapling, or sewing.

[0103] In some embodiments, the mesh may be labeled. This labeling can be done in any suitable manner and at any suitable location on the mesh. In some embodiments, labeling can be done using screen printing, using altered weaving or knotting patterns, using different colored threads, or other means. The labeling can indicate information about the mesh. This information may include part numbers, donor ID numbers, numbers indicating the order of use in the procedure or implant size, letters or words, etc. In some embodiments, the mesh may be a specific color to help provide proper orientation of the mesh before or during filling and to confirm that the mesh's multiple protrusions and / or multiple recesses are oriented to optimize their engagement. In some embodiments, a portion or the entire mesh is colored blue, purple, pink, orange, yellow, green, or red.

[0104] The mesh can be closed after it has been wound to at least partially or completely encapsulate the bone material. Therefore, the bone implant can be provided unfilled and unsealed. After the material to be delivered is placed in the wound bone implant, the mesh of the bone implant can be permanently or temporarily closed by one or more strands configured to be tied or otherwise secured. Alternatively, temporary closure can be achieved by folding and locking, tightening, adhesives, or other means. A temporarily closed bone implant can be opened during surgical placement without damaging the mesh to add or remove material from the bone implant.

[0105] In some implementations, the wound mesh can completely encapsulate the bone material, wherein the wound mesh surrounds the entire bone material (e.g., bone particles, bone cement, etc.) to completely encapsulate the bone material, such as... Figure 7B As shown. In some embodiments, the mesh may partially wind around and partially enclose bone material (e.g., bone particles, bone cement, etc.), wherein the mesh surrounds a portion of the bone material, leaving a portion of the bone material unenclosed by the mesh, such as... Figure 7C As shown.

[0106] Bone materials for bone implants may include fully demineralized bone fibers and superficially demineralized bone fragments. Bone materials also include fibers, powders, fragments, triangular prisms, spheres, cubes, cylinders, debris, or other shapes with irregular or random geometry. These may comprise, for example, “substantially demineralized,” “partially demineralized,” or “fully demineralized” cortical and / or cancellous bone. They also include superficially demineralized material, wherein the surface of the bone structure is substantially demineralized, partially demineralized, or fully demineralized, while the bulk of the bone structure is fully mineralized.

[0107] In some embodiments, the bone implant is configured to be self-sealing or sealed via chemical fusion, heat treatment, self-fusion materials, self-adhesive materials, adhesives, or combinations thereof, and encapsulates bone material. In some embodiments, adhesives that may be used include, but are not limited to, cyanoacrylates (such as tissue adhesives like B Braun, which is n-butyl-2-cyanoacrylate; or Dermabond, which is 2-octylcyanoacrylate), epoxy compounds, dental resin sealants, dental resin adhesives, glass ionomer adhesives, polymethyl methacrylate, gelatin-resorcinol-formaldehyde glue, collagen-based glues, inorganic binders such as zinc phosphate, magnesium phosphate, or other phosphate-based adhesives, zinc carboxylate, L-DOPA (3,4-dihydroxy-L-phenylalanine), proteins, carbohydrates, glycoproteins, mucopolysaccharides, other polysaccharides, hydrogels, protein-based binders such as fibrin glue and mussel-derived adhesive proteins, and any other suitable substances. In some embodiments, the bone implant can be sealed by mechanical means such as zippers, sutures, staples, pins, snaps, clips, or combinations thereof. In some embodiments, the bone implant can be sealed by applying a volatile or water-soluble solvent to the mesh material, which temporarily softens the mesh or causes the surface of the mesh to dissolve, allowing the mesh to bond and adhere to adjacent meshes. Once the volatile or water-soluble solvent is removed from the application site, the mesh will harden or settle, thereby forming a bond between the two parts of the mesh at the solvent application site.

[0108] In some implementations, the wound mesh may remain closed or sealed for approximately 1 to approximately 2 hours. When used with wet or dry bone materials, the temporary or permanent closure or seal of the mesh should be compatible and still functional.

[0109] In some embodiments, the bone implant is configured to be self-sealing or sealed via chemical fusion, heat treatment, self-fusion materials, self-adhesive materials, adhesives, or combinations thereof, and encapsulates bone material. In some embodiments, adhesives that may be used include, but are not limited to, cyanoacrylates (such as tissue adhesives like B Braun, which is n-butyl-2-cyanoacrylate; or Dermabond, which is 2-octylcyanoacrylate), epoxy compounds, dental resin sealants, dental resin adhesives, glass ionomer adhesives, polymethyl methacrylate, gelatin-resorcinol-formaldehyde glue, collagen-based glues, inorganic binders such as zinc phosphate, magnesium phosphate, or other phosphate-based adhesives, zinc carboxylate, L-DOPA (3,4-dihydroxy-L-phenylalanine), proteins, carbohydrates, glycoproteins, mucopolysaccharides, other polysaccharides, hydrogels, protein-based binders such as fibrin glue and mussel-derived adhesive proteins, and any other suitable substances. In some implementations, bone implants can be sealed by mechanical means such as zippers, sutures, nails, pins, snaps, clips, or combinations thereof.

[0110] In some implementations, bioattachment can be achieved through mechanisms that promote tissue inward growth, such as porous coatings or hydroxyapatite-tricalcium phosphate (HA / TCP) coatings. Typically, hydroxyapatite binds through the biological action of new tissue formation. Porous inward growth surfaces, such as titanium alloy materials or porous tantalum metals or trabecular metals in beaded coatings, can be used, and attachment is promoted at least by inducing bone growth through the porous implant surface. These mechanisms may be referred to as bioattachment mechanisms. In some implementations, bone implants can be attached to tissue structures via wraps, sutures, silk threads, strips, elastic bands, cables or cable clips, or combinations thereof, or another fastener.

[0111] In other embodiments, suitable materials for forming the mesh of the bone implant include natural materials, synthetic polymeric resorbable materials, synthetic polymeric non-resorbable materials, and other materials. Natural mesh materials include filaments, extracellular matrix (such as DBM, collagen, ligaments, tendon tissue, or others), filament-elastin, elastin, collagen, and cellulose. Synthetic polymeric resorbable materials include poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-glycolic acid) (PLGA), poly(p-dioxanone), PVA, polyurethane, polycarbonate, etc. In some embodiments, the mesh may be made of hydroxyapatite, calcium phosphate, ceramics, or combinations thereof.

[0112] In some embodiments, the mesh may be made of shape-memory polymers and / or alloys to allow the mesh to move from a planar configuration to a wound configuration to at least partially encapsulate the bone material without the need for locking or tying mechanisms. Shape-memory polymers include, but are not limited to, polyethers, polyacrylates, polyamides, polysiloxanes, polyurethanes, polyetheramides, polyurethane / urea, polyether esters, polynorbornene, crosslinked polymers (such as crosslinked polyethylene and crosslinked poly(cyclooctene)), inorganic-organic hybrid polymers, and copolymers such as urethane / butadiene copolymers and styrene-butadiene copolymers.

[0113] The mesh may be absorbable and / or reabsorbable, and is made of at least one material selected from, but not limited to, poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), polydioxanone (PDO), allogeneic collagen, xenogeneic collagen, hydroxyapatite, calcium phosphate, ceramics, or combinations thereof. When formed from absorbable or reabsorbable materials, the mesh may be reabsorbed substantially within 2 weeks, 3 weeks, 4 weeks, 12 weeks, 16 weeks, 20 weeks, 24 weeks, 28 weeks, 32 weeks, 36 weeks, 40 weeks, 44 weeks, 48 ​​weeks, 52 weeks, or any other suitable timeframe. In some embodiments, the mesh may maintain its strength during this timeframe. In some embodiments, reabsorption of the mesh is expected approximately 6 months post-implantation. In various embodiments, the mesh is biocompatible, meaning that it is expected not to cause irritation or inflammation of surrounding tissues. To ensure biocompatibility and proper reabsorption, the pH of the surrounding tissue should be greater than about 3. Generally, the shelf life of the mesh expected to be used in the implants described in this disclosure varies from about 2 years to 4 years. In some embodiments, the mesh may remain closed to at least partially encapsulate the bone material for at least 1 to 2 hours.

[0114] In some embodiments, the web itself may be adhesive, for example, when an adhesive is applied to the web or portions thereof to allow the web to remain in a wound configuration. The adhesive may be, for example, a bioadhesive, glue, binder, cyanoacrylate, silicone, hot melt adhesive, and / or cellulose binder.

[0115] The material and configuration of the mesh can be selected or adjusted based on desired release characteristics. Specific properties of the adjustable mesh include thickness, permeability, porosity, strength, flexibility, and / or elasticity. In some embodiments, the thickness and porosity of the mesh may contribute to its strength, flexibility, and elasticity. In some embodiments, the mesh may be made of a soft, moldable, adhesive, and / or tacky material to facilitate the placement and filling of bone implants into the surgical site.

[0116] The average molecular weight of the polymer used to prepare the network can be from about 1,000 g / mol to about 10,000,000 g / mol; or from about 1,000 g / mol to about 1,000,000 g / mol; or from about 5,000 g / mol to about 500,000 g / mol; or from about 10,000 g / mol to about 100,000 g / mol; or from about 20,000 g / mol to about 50,000 g / mol. In some embodiments, the polymer has a molecular weight of 1,000 Daltons, 2,000 Daltons, 3,000 Daltons, 4,000 Daltons, 5,000 Daltons, 6,000 Daltons, 7,000 Daltons, 8,000 Daltons, 9,000 Daltons, 10,000 Daltons, 15,000 Daltons, 20,000 Daltons, 25,000 Daltons, 30,000 Daltons, 35,000 Daltons, 40,000 Daltons, or 45,000 Daltons. 00 Daltons, 50,000 Daltons, 55,000 Daltons, 60,000 Daltons, 65,000 Daltons, 70,000 Daltons, 75,000 Daltons, 80,000 Daltons, 85,000 Daltons, 90,000 Daltons, 95,000 Daltons, 100,000 Daltons, 125,000 Daltons, 150,000 Daltons, 175,000 Daltons, 200,000 Daltons, 225,000 Daltons 250,000 Daltons, 275,000 Daltons, 300,000 Daltons, 325,000 Daltons, 350,000 Daltons, 375,000 Daltons, 400,000 Daltons, 425,000 Daltons, 450,000 Daltons, 475,000 Daltons, 500,000 Daltons, 525,000 Daltons, 550,000 Daltons, 575,000 Daltons, 600,000 Daltons, 625,000 Daltons, 650,000 Daltons, 675,000 Daltons, 700,000 Daltons, 725,000 Daltons, 750,000 Daltons, 775,000 Daltons, 800,000 Daltons, 825,000 Daltons, 850,000 Daltons, 875,000 Daltons, 900,000 Daltons, 925,000 Daltons, 950,000 Daltons, 975,000 Daltons and / or 1,000,000 Daltons.

[0117] The mesh can have varying degrees of permeability. It can be permeable, semi-permeable, or impermeable. Permeability can be related to cells, fluids, proteins, growth factors, bone morphogenetic proteins, or other substances. The mesh can be 1% to about 30% permeable, about 30% to about 70% permeable, or about 70% to about 95% permeable. The mesh can be 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% permeable.

[0118] In various embodiments, the mesh may encapsulate or partially encapsulate bone material (e.g., DBM). In some embodiments, the mesh comprises a polymer matrix that may have DBM fibers and / or DBM powder within its threads, these DBM fibers and / or DBM powder suspended within the polymer matrix to facilitate cell translocation in and out of the mesh bag to induce bone growth at the surgical site. In other embodiments, the mesh also comprises mineralized bone fibers suspended within the polymer matrix. In some embodiments, DBM powder is suspended within the polymer matrix between the DBM fibers and the mineralized bone fibers. In some embodiments, DBM powder is suspended between the DBM fibers within the polymer matrix to reduce and / or eliminate gaps between the fibers. In some embodiments, DBM powder is suspended between the DBM fibers within the polymer matrix to improve osteoinductive properties that promote bone fusion (e.g., interspinous fusion).

[0119] In some embodiments, the polymer matrix comprises a bio-erosive, bioabsorbable, and / or biodegradable biopolymer that can provide immediate or sustained release. Examples of suitable sustained-release biopolymers include, but are not limited to, poly(α-hydroxy acid), poly(lactide-co-glycolic acid) (PLGA), polylactide (PLA), polyglycolic acid (PG), polyethylene glycol (PEG), conjugates of poly(α-hydroxy acid), polyorthoesters (POE), polyaspirin, polyphosphazene, collagen, starch, pregelatinized starch, hyaluronic acid, chitosan, gelatin, alginate, albumin, fibroin, and vitamin E compounds (such as α-tocopheryl acetate, d-α-...). Tocopheryl succinate), D,L-lactide or L-lactide, caprolactone, dextran, vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBT copolymer (polyactive), PEO-PPO-PAA copolymer, PLGA-PEO-PLGA, PEG-PLG, PLA-PLGA, poloxamer 407, PEG-PLGA-PEG triblock copolymer, SAIB (sucrose isobutyrate acetate), or combinations thereof. mPEG and / or PEG can be used as plasticizers for PLGA, but other polymers / excipients can be used to achieve the same effect. mPEG imparts ductility to the polymer.

[0120] In some embodiments, these biopolymers may also be coated onto the mesh to provide a desired release profile or inward tissue growth. In some embodiments, the coating thickness can range from thinner coatings, such as about 5 micrometers, 10 micrometers, 15 micrometers, 20 micrometers, 25 micrometers, 30 micrometers, 35 micrometers, 40 micrometers, 45 micrometers, or 50 micrometers, to thicker coatings, such as 60 micrometers, 65 micrometers, 70 micrometers, 75 micrometers, 80 micrometers, 85 micrometers, 90 micrometers, 95 micrometers, or 100 micrometers, to delay the release of material from the bone implant. In some embodiments, the coating on the mesh ranges from about 5 micrometers to about 250 micrometers or from about 5 micrometers to about 200 micrometers. In some embodiments, the mesh comprises a polymer coating, and the coating contains a bioactive agent or bioactive material.

[0121] The mesh can be manufactured using any fully absorbable or reabsorbable material, such as, for example, absorbable polymers, such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), polydioxanone (PDO), allogeneic collagen, xenogeneic collagen, ceramics, hydroxyapatite, calcium phosphate, or combinations thereof. The mesh can be made from monofilament or multifilament yarns or threads, and can be manufactured using knitting, weaving, or nonwoven, such as felted or dot-bonded, or manufactured using additive manufacturing methods (e.g., 3D printing). U.S. Patents 10,064,726 and 10,442,175, incorporated herein by reference as fully described herein, describe 3D printing techniques that can be used to manufacture the mesh implants for bone delivery described in this application. The mesh has sufficiently large pores to not impede cell transport and new bone formation. However, the pores are small enough to adequately contain the graft material at the implantation site. Bone implants can come in various shapes and are equipped with instruments designed for easy use and assembly during surgery. Streamlined assembly is possible. Customization of the diameter and width of bone implants allows them to be used in a variety of bone fusion repair surgeries using smaller grafts, such as minimally invasive midline lumbar fusion, posterior cervical fusion, and maxillofacial reconstruction.

[0122] In some embodiments, the various components of the mesh comprise poly(lactide-co-glycolic acid) (PLGA), polylactide (PLA), polyglycolic acid (PGA), D-lactide, D,L-lactide, L-lactide, D,L-lactide-co-ε-caprolactone, D,L-lactide-co-glycolic acid-co-ε-caprolactone, L-lactide-co-ε-caprolactone, hydroxyapatite, calcium phosphate, ceramics, or combinations thereof.

[0123] In some implementations, the mesh also includes bone morphogenetic protein (BMP), growth factors, antibiotics, angiogenesis-promoting materials, bioactive agents, or other actively released materials.

[0124] The mesh can be used to deliver substances comprising any suitable biocompatible material. In specific embodiments, the mesh can be used to deliver surface-demineralized bone fragments, optionally with a predetermined particle size, optionally compressed fully demineralized bone fibers, and / or allogeneic grafts. For embodiments where the substance is biological, the substance can be autologous, allogeneic, xenogeneic, or genetically modified. Other suitable materials that can be placed in the mesh include, for example, proteins, nucleic acids, carbohydrates, lipids, collagen, allogeneic bone grafts, autologous bone grafts, cartilage stimulating substances, allogeneic cartilage grafts, TCP, hydroxyapatite, calcium sulfate, polymers, nanofiber polymers, growth factors, growth factor carriers, tissue growth factor extracts, DBM, dentin, bone marrow aspirate, bone marrow aspirate in combination with various bone-inducing or osteoconductive carriers, lipid-derived or bone marrow-derived adult stem cell concentrates, umbilical cord-derived stem cells, adult or embryonic stem cells in combination with various bone-inducing or osteoconductive carriers, transfected cell lines, osteoblasts derived from the periosteum, combinations of bone and cartilage stimulating materials, morphological or partially morphological cells from osteoblast or chondrocyte lineages, or combinations of any of the above.

[0125] According to some implementation schemes, the material to be placed in the hollow area of ​​the wound net may be supplemented, further processed, or chemically modified with one or more bioactive agents or bioactive compounds. As used herein, a bioactive agent or bioactive compound refers to a compound or entity that alters, inhibits, activates, or otherwise affects a biological or chemical event. For example, bioactive agents may include, but are not limited to: osteogenic or chondrogenic proteins or peptides; DBM powder; collagen, insoluble collagen derivatives, etc., and soluble solids and / or liquids dissolved therein; anti-AIDS substances; anticancer substances; antimicrobial agents and / or antibiotics, such as erythromycin, bacitracin, neomycin, penicillin, polymyxin B, tetracycline, biomycin, chloramphenicol, and streptomycin, cefazolin, ampicillin, azactam, tobramycin, clindamycin, gentamicin, etc.; immunosuppressants; antiviral substances, such as substances effective against hepatitis; enzyme inhibitors; hormones; neurotoxins; opioids; hypnotics; antihistamines; Amines; lubricants; sedatives; anticonvulsants; muscle relaxants and anti-Parkinson's substances; antispasmodics and muscle contractile agents, including channel blockers; miotics and anticholinergics; antiglaucoma compounds; antiparasitic and / or antiprotozoal compounds; modulators of cell-extracellular matrix interactions, including cell growth inhibitors and antiadhesion molecules; vasodilators; inhibitors of DNA, RNA, or protein synthesis; antihypertensives; analgesics; antipyretics; steroidal and nonsteroidal anti-inflammatory agents; anti-angiogenic factors; angiogenic factors and polymer carriers containing such factors; antisecretory factors; anticoagulants and / or antithrombotic agents; local anesthetics; ophthalmic drops; prostaglandins; Antidepressants; antipsychotics; antiemetics; imaging agents; biocidal / bioinhibitory sugars, such as dextran, glucose, etc.; amino acids; peptides; vitamins; inorganic elements; cofactors in protein synthesis; endocrine tissues or tissue fragments; synthetic compounds; enzymes, such as alkaline phosphatase, collagenase, peptidase, oxidase, etc.; polymeric cell scaffolds with parenchymal cells; collagen lattices; antigens; cytoskeleton agents; cartilage fragments; living cells, such as chondrocytes, bone marrow cells, mesenchymal stem cells; natural extracts; genetically engineered or otherwise modified living cells; expanded or cultured cells; DNA delivered by plasmids, viral vectors, or other members; tissue transplants. Implants; autologous tissues, such as blood, serum, soft tissue, bone marrow, etc.; biological adhesives; bone morphogenetic proteins (BMPs, including BMP-2); bone-inducing factor (IFO); fibronectin (FN); endothelial growth factor (ECGF); vascular endothelial growth factor (VEGF); cementum attachment extract (CAE); ketoselin; human growth hormone (HGH); animal growth hormone; epidermal growth factor (EGF); interleukins, such as interleukin-1 (IL-1) and interleukin-2 (IL-2); human alpha thrombin; transforming growth factor (TGF-β); insulin-like growth factor (IGF-1, IGF-2);Parathyroid hormone (PTH); platelet-derived growth factor (PDGF); fibroblast growth factor (FGF, BFGF, etc.); periodontal ligament chemokine (PDLGF); enamel matrix protein; growth and differentiation factor (GDF); hedgehog protein family; protein receptor molecules; small peptides derived from the above growth factors; bone promoters; cytokines; growth hormones; bone digests; antitumor agents; cell inducers and adhesion agents; immunosuppressants; permeability enhancers, such as fatty acid esters, such as polyethylene glycol laurate, myristate and stearate monoesters, enamine derivatives, α-ketoaldehydes; and nucleic acids.

[0126] In some embodiments, the bioactive agent may be a drug. In some embodiments, the bioactive agent may be a growth factor, cytokine, extracellular matrix molecule, or fragment or derivative thereof, such as a protein or peptide sequence, like RGD.

[0127] In various implementation schemes, the mesh material of the bone implant may have an elastic modulus. For example... Figure 13A As shown, in some aspects, the main body portion 80 of the cover 18 (or net 32) may be made of inelastic yarn, while the closure portion 82 may be made of either inelastic or elastic yarn to ensure consistent winding around the main body portion 80. In some embodiments, the closure portion 82 may have approximately 1 × 10⁻⁶ mm. 2 Approximately 6×10 5 dynes / cm 2 or 2×10 4 Approximately 5×10 5 dynes / cm 2 or 5×10 4 Approximately 5×10 5 dynes / cm 2 The elastic modulus. In some embodiments, the closure portion will be more elastic, and when the cover is rolled up, the closure portion may wrap around the body portion having a narrower weave, and then the body portion may be positioned within the separate wider weave of the closure portion to at least partially encapsulate the bone material within the cover in the rolled-up configuration.

[0128] The material may possess functional properties. Alternatively, other materials with functional properties may be incorporated into the mesh. Functional properties may include radiation impermeability, bactericidal activity, release of material sources, adhesiveness, etc. Such properties may be imparted substantially throughout the mesh or at certain locations or portions of the mesh.

[0129] Suitable radiopaque materials include, for example, ceramics, mineralized bone, ceramic / calcium phosphate / calcium sulfate, metal particles, fibers, and iodinated polymers (see, for example, WO 2007 / 143698). Polymer materials can be used to form a mesh and made radiopaque by iodization, as taught, for example, in U.S. Patent 6,585,755, the entire contents of which are incorporated herein by reference. Other techniques for increasing the radiopaqueness of polymers by incorporating biocompatible metals or metal salts can also be used. Suitable bactericidal materials may include, for example, trace metal elements. In some embodiments, trace metal elements may also promote bone growth.

[0130] In some embodiments, the net may comprise a material that becomes sticky when wetted. This material may be, for example, a protein- or gelatin-based material. Tissue adhesives, including mussel adhesive proteins and cyanoacrylates, may be used to impart adhesiveness to the net. In other examples, alginate or chitosan materials may be used to impart adhesiveness to the net. In other embodiments, an adhesive substance or material may be placed on a portion of the net or a specific area of ​​the net to anchor that portion or area of ​​the net in the appropriate position at the implantation site.

[0131] Bone materials

[0132] The bone material can be natural or synthetic (e.g., tricalcium phosphate and / or hydroxyapatite). In various embodiments, the bone material can be granular, such as bone fragments, powder, or fibers. If the bone is demineralized, it can be granulated before, during, or after demineralization. In some embodiments, the bone can be monolithic and may not be microparticles.

[0133] Before or after demineralization, bone can be ground and milled or otherwise processed into particles of suitable size. The particles can be granular (e.g., powder) or fibrous. The terms grinding or milling are not intended to limit the production of a particular type of particle and can refer to the production of granular or fibrous particles. In some embodiments, the particle size can be greater than 25 micrometers, such as in the range of about 25 micrometers to about 2000 micrometers, or about 25 micrometers to about 500 micrometers, or about 200 micrometers to about 1000 micrometers. In some embodiments, the bone particle size is less than 100 micrometers. In some embodiments, the bone particle size is less than 500 micrometers.

[0134] After grinding, the bone particles can be sieved to select those of the desired size. In some embodiments, the particles can be sieved using 25-micron, 50-micron, 75-micron, 100-micron, 125-micron, 150-micron, 175-micron, and / or 200-micron sieves.

[0135] In some embodiments, the bone material comprises DBM and / or mineralized bone. In some embodiments, the size of the bone material is less than 25 micrometers. In some embodiments, the particle size of the bone material is about 1 micrometer, 2 micrometer, 3 micrometer, 4 micrometer, 5 micrometer, 6 micrometer, 7 micrometer, 8 micrometer, 9 micrometer, 10 micrometer, 11 micrometer, 12 micrometer, 13 micrometer, 14 micrometer, 15 micrometer, 16 micrometer, 17 micrometer, 18 micrometer, 19 micrometer, 20 micrometer, 21 micrometer, 22 micrometer, 23 micrometer, 24 micrometer and / or 25 micrometer.

[0136] In various embodiments, bone meal, bone flakes, and / or DBM and / or mineralized bone fibers have an adhesive outer surface, allowing the bone material to adhere to the DBM and / or mineralized bone fibers. In various embodiments, the bone meal is naturally adhesive. In some embodiments, an adhesive is applied to the bone meal and / or bone fibers, said adhesive including bioadhesives, adhesives, binders, cyanoacrylates, silicones, hot melt adhesives, and / or cellulose binders. In various embodiments, the adhesive can be applied to the surface of the bone meal by spraying or brushing. In some embodiments, a charge is applied to the fibers and an opposite charge is applied to the bone meal (i.e., electrostatic deposition). The bone meal will be attracted and firmly adhered to the fiber surface. Any of these application techniques can be repeated once or multiple times to accumulate a relatively thick layer of adhesive bone meal on the fiber surface.

[0137] Bone meal can be directly applied to DBM fibers and / or fully mineralized fibers, fragments, and the mixture can be placed in a mesh. In some embodiments, the bone material inserted into the mesh contains pores with a pore size of about 0.5 micrometers to about 2,000 micrometers. In some embodiments, the bone material inserted into the mesh contains pores with pore sizes of about 0.5 micrometers, 5 micrometers, 50 micrometers, 100 micrometers, 150 micrometers, 200 micrometers, 250 micrometers, 300 micrometers, 350 micrometers, 400 micrometers, 450 micrometers, 500 micrometers, 550 micrometers, 600 micrometers, 650 micrometers, 700 micrometers, 750 micrometers, 800 micrometers, 850 micrometers, 900 micrometers, 950 micrometers, 1,000 micrometers, 1,050 micrometers, etc. The pore size ranges from 0 micrometers, 1,100 micrometers, 1,150 micrometers, 1,200 micrometers, 1,250 micrometers, 1,300 micrometers, 1,350 micrometers, 1,400 micrometers, 1,450 micrometers, 1,500 micrometers, 1,550 micrometers, 1,600 micrometers, 1,650 micrometers, 1,700 micrometers, 1,750 micrometers, 1,800 micrometers, 1,850 micrometers, 1,900 micrometers, 1,950 micrometers to about 2,000 micrometers. In some embodiments, the pore size of the bone material is uniform. In some embodiments, the pore size of the bone material is non-uniform and includes various pore sizes ranging from 0.5 micrometers to about 2,000 micrometers. Alternatively, DBM fibers, sheets, and DBM powder can be placed in a polymer (e.g., collagen) and inserted into a bone implant.

[0138] After scraping, grinding, or other techniques used to obtain them, bone materials are demineralized to reduce their inorganic content to very low levels, in some embodiments, to no more than about 5% by weight of residual calcium and no more than about 1% by weight of residual calcium. Demineralization of bone materials typically results in some degree of shrinkage.

[0139] The bone used in the methods described herein can be an autologous graft, an allogeneic graft, or a xenograft. In various embodiments, the bone can be cortical bone, cancellous bone, or cortical-cancellous bone. Although demineralized bone matrix is ​​specifically discussed herein, bone matrix treated according to the teachings herein can be undemineralized, demineralized, partially demineralized, or superficially demineralized. This discussion applies to demineralized, partially demineralized, and superficially demineralized bone matrices. In one embodiment, the demineralized bone is derived from bovine or human bone. In another embodiment, the demineralized bone is derived from human bone. In one embodiment, the demineralized bone is derived from the patient's bone (autologous bone). In another embodiment, the demineralized bone is derived from a different animal of the same species (including cadavers) (allogeneic bone graft).

[0140] In some embodiments, the bone material may be a combination of patient-generated autologous bone and other bone materials such as, for example, allogeneic grafts, allogeneic graft DBM, ceramic, and / or any one of the aforementioned bone materials. In some embodiments, the combined bone material may have a 50:50 ratio of autologous bone to other bone material. In some embodiments, the combined bone material may have any ratio of autologous bone to other bone material, including but not limited to 25:75, 75:25, 10:90, 90:10, 20:80, 80:20, 30:70, 70:30, 40:60, or 60:40.

[0141] In some embodiments, the bone material may be approximately 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, etc. 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% to approximately 100% of patients received autologous bone grafts, additional bone materials, or combinations thereof.

[0142] Bone can be demineralized using any suitable method. Demineralization of bone material can be performed according to known conventional procedures. For example, in a preferred demineralization procedure, bone material suitable for the implantable compositions of this application undergoes an acid demineralization step followed by a degreasing / sterilization step. The bone material is immersed in acid, achieving demineralization over time. Acids that can be used in this step include inorganic acids, such as hydrochloric acid; and organic acids, such as peracetic acid, acetic acid, citric acid, or propionic acid. The depth of demineralization into the bone surface can be controlled by adjusting the treatment time, the temperature of the demineralization solution, the concentration of the demineralization solution, the intensity of agitation during treatment, and other applied forces, such as vacuum, centrifuge, pressure, and other factors as known to those skilled in the art. Therefore, in various embodiments, the bone material can be completely demineralized, partially demineralized, or surface-demineralized.

[0143] Following acid treatment, the bone is rinsed with sterile water for injection, buffered to the final predetermined pH value, and then finally rinsed with water for injection to remove residual acid and buffer, or washed with water to remove residual acid and thus raise the pH. After demineralization, the bone material is immersed in a solution to degrease it. The degreasing / disinfectant solution is an aqueous solution of ethanol, which is a good solvent for lipids, and water is a good hydrophilic carrier, allowing the solution to penetrate deeper into the bone. The aqueous ethanol solution also disinfects the bone by killing nutrient microorganisms and viruses. Typically, at least about 10 to 40% by weight of water (i.e., about 60 to 90% by weight of the degreasing agent, such as ethanol) should be present in the degreasing / disinfectant solution to achieve optimal lipid removal and disinfection in the shortest possible time. The concentration range of the degreasing solution is about 60 to 85% by weight of ethanol or about 70% by weight of ethanol.

[0144] Furthermore, according to this application, the DBM material can be used immediately for the preparation of bone implants, or it can be stored under sterile conditions, advantageously stored in a critical point dry state prior to such preparation. In one embodiment, the bone material can retain some of its original mineral content, allowing the composition to be imaged using radiographic techniques.

[0145] In various embodiments, this application also provides bone matrix compositions comprising critical point drying (CPD) fibers. DBM comprises a collagen matrix of bone and acid-insoluble proteins, including bone morphogenetic proteins (BMPs) and other growth factors. DBM can be formulated as microparticles, microspheres, spheres, gels, sponge materials, or putties, and can be freeze-dried for storage. Sterilization procedures used to prevent the spread of disease may reduce the activity of beneficial growth factors in DBM. DBM provides an initial osteoconductive matrix and exhibits a degree of osteoinductive potential, inducing the infiltration and differentiation of osteoprogenitor cells from surrounding tissues.

[0146] DBM formulations have been used in orthopedic medicine for many years to promote bone formation. For example, DBMs have been found to repair fractures, fuse vertebrae, perform joint replacement surgery, and treat bone destruction caused by underlying conditions such as rheumatoid arthritis. DBMs are thought to promote bone formation in vivo through osteoconduction and osteoinduction processes. The osteoinductive effect of implanted DBM compositions is believed to be caused by the presence of active growth factors present on a separated collagen-based matrix. These factors include members of the TGF-β, IGF, and BMP protein families. Examples of osteoinductive factors include TGF-β, IGF-1, IGF-2, BMP-2, BMP-7, parathyroid hormone (PTH), and angiogenic factors. Other osteoinductive factors, such as osteocalcin and osteopontin, may also be present in DBM formulations. Other unnamed or undiscovered osteoinductive factors may also be present in DBMs.

[0147] In various embodiments, the DBM provided in the kits, implants, and methods described in this application is prepared from elongated bone fibers that have undergone critical point drying (CPD). The elongated CPD bone fibers used in this application are generally characterized by having a relatively high average length-to-width ratio, also known as aspect ratio. In various embodiments, the aspect ratio of the elongated bone fibers is at least about 50:1 to at least about 1000:1. Such elongated bone fibers can be readily obtained by any of several methods, such as by grinding or cutting the entire surface of the bone or a relatively large portion of the bone.

[0148] In other embodiments, the fiber length may be at least about 3.5 cm and the average width may be about 20 mm to about 1 cm. In various embodiments, the elongated fiber may have an average length of about 3.5 cm to about 6.0 cm and an average width of about 20 mm to about 1 cm. In other embodiments, the elongated fiber may have an average length of about 4.0 cm to about 6.0 cm and an average width of about 20 mm to about 1 cm.

[0149] In other embodiments, the diameter or average width of the elongated fibers is, for example, no greater than about 1.00 cm, no greater than 0.5 cm, or no greater than about 0.01 cm. In other embodiments, the diameter or average width of the fibers may be from about 0.01 cm to about 0.4 cm or from about 0.02 cm to about 0.3 cm.

[0150] In another embodiment, the aspect ratio of the fibers may be from about 50:1 to about 950:1, from about 50:1 to about 750:1, from about 50:1 to about 500:1, from about 50:1 to about 250:1; or from about 50:1 to about 100:1. The aspect ratio of the fibers according to this disclosure may be from about 50:1 to about 1000:1, from about 50:1 to about 950:1, from about 50:1 to about 750:1, from about 50:1 to about 600:1, from about 50:1 to about 350:1, from about 50:1 to about 200:1, from about 50:1 to about 100:1, or from about 50:1 to about 75:1.

[0151] In some embodiments, the fragment-to-fiber ratio is about 90:10, 80:20, 75:25, 70:30, 60:40, 50:50, 40:60, 30:70, 25:75, 20:80, and / or 10:90. In various embodiments, the fragment-to-fiber ratio of the surface-demineralized material is about 90:10, 80:20, 75:25, 70:30, 60:40, 50:50, 40:60, 30:70, 25:75, 20:80, and / or 10:90. In some implementations, the ratio of surface-demineralized fragments to fully demineralized fibers is approximately 90:10, 80:20, 75:25, 70:30, 60:40, 50:50, 40:60, 30:70, 25:75, 20:80, and / or 10:90.

[0152] In some embodiments, the DBM fibers have a thickness of about 0.5 mm to 4 mm. In various embodiments, the DBM fibers have a thickness of about 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm, and / or 4 mm. In various embodiments, the ratio of DBM fibers to DBM powder is about 40:60 to about 90:10 W / W, W / V, or V / V. In some embodiments, the ratio of mineralized bone fibers to DBM powder is about 25:75 to about 75:25 W / W, W / V, or V / V. In various embodiments, the bone implant comprises DBM fibers and mineralized fibers in a ratio of 40:60 to about 90:10 W / W, W / V, or V / V. In some embodiments, the ratio of DBM fibers to DBM powder, the ratio of mineralized bone fibers to DBM powder, and / or the ratio of DBM fibers to mineralized fibers is from 5:95 to approximately 95:5 W / W, W / V, or V / V. In some embodiments, the ratio of DBM fibers to DBM powder, the ratio of mineralized bone fibers to DBM powder, and / or the ratio of DBM fibers to mineralized fibers is 5:95, 10:90, 15:85, 20:80, 25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, 90:10, and / or 95:5 W / W, W / V, or V / V.

[0153] In some embodiments, the bone material includes demineralized bone material, which includes demineralized bone, fibers, powder, fragments, triangular prisms, spheres, cubes, cylinders, debris, or other shapes with irregular or random geometry. These may comprise, for example, “substantially demineralized,” “partially demineralized,” or “completely demineralized” cortical and / or cancellous bone. These also include surface demineralized material, wherein the surface of the bone structure is substantially demineralized, partially demineralized, or completely demineralized, while the bulk of the bone structure is fully mineralized.

[0154] In various embodiments, the bone material comprises fully demineralized DBM fibers and surface-demineralized bone fragments. In some embodiments, the ratio of fully demineralized DBM fibers to surface-demineralized bone fragments is from 5:95 to approximately 95:5 fiber-to-fraction ratio. In some embodiments, the ratio of fully demineralized DBM fibers to surface-demineralized bone fragments is 5:95, 10:90, 15:85, 20:80, 25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, 90:10, and / or 95:5 fiber-to-fraction ratio. In various embodiments, the fully demineralized DBM fibers have a thickness of approximately 0.5-4 mm. In various implementations, the full DBM fibers have a thickness of approximately 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm and / or 4 mm.

[0155] In various embodiments, the fibers and / or powder are surface DBM. In some embodiments, the fibers and / or powder are surface DBM cortical allografts. In various embodiments, surface demineralization involves surface demineralization at least to a certain depth. For example, surface demineralization of an allograft can be from about 0.25 mm, 0.5 mm, 1 mm, 1.5 mm, 2.0 mm, 2.5 mm, 3.0 mm, 3.5 mm, 4 mm, 4.5 mm to about 5 mm. The edges of the bone fibers and / or powder may be further machined into any shape or include features such as grooves, protrusions, depressions, etc., to help improve fit and limit any movement or micromotion, thereby aiding in fusion and / or osteoinduction.

[0156] DBM is typically dried, for example by freeze-drying or solvent drying, to store and maintain it under viable conditions for implantation. Furthermore, each of these procedures is believed to reduce the overall surface area structure of bone. Understandably, structural damage to the outer surface reduces the overall surface area. These physical alterations to the surface and the reduction in surface area may affect cell connectivity, migration, proliferation, and differentiation. The surface's affinity for growth factors and the kinetics of growth factor release from the surface may also be altered.

[0157] Therefore, in some embodiments, methods are provided for drying bone to store and maintain it under viable conditions for implantation, said implantation maintaining or increasing the surface area of ​​the bone. In one embodiment, critical point drying (CPD) technology is used to treat the bone matrix, thereby reducing damage to the bone surface. Although critical point drying has been specifically described, it should be understood that supercritical point treatment may be used in alternative embodiments. In various embodiments utilizing CPD, the percentage of collagen fibrils on the bone surface remains unchanged to about 15% or less of residual moisture content after drying. In some embodiments, the bone matrix has about 8% or less of residual moisture content after drying. In some embodiments, the bone matrix has about 6% or less of residual moisture content after drying. In some embodiments, the bone matrix has about 3% or less of residual moisture content after drying.

[0158] Evaporative drying and freeze-drying of samples can cause surface structure deformation and collapse, resulting in a decrease in surface area. It is not desirable to be bound by any particular theory, but it is thought that this deformation and structural collapse occurs because when a substance crosses the boundary from liquid to gas, the evaporation of that substance reduces the volume of the liquid. When this happens, the surface tension at the solid-liquid interface pulls on any structure to which the liquid is attached. This surface tension often causes the breakage of fine surface structures. This damage may be caused by the effect of surface tension on the liquid / gas interface. Critical point drying is a technique that avoids the effect of surface tension on the liquid / gas interface by essentially preventing the formation of a liquid / gas interface. Critical point or supercritical drying does not cross any phase boundary but passes through the supercritical region, where the distinction between gas and liquid no longer applies. Therefore, materials dehydrated using critical point drying are not subjected to destructive surface tension. When the critical point of a liquid is reached, it can transition from liquid to gas without a sudden change of state. Critical point drying can be used with bone matrix for phase transitions from liquid to dry gas without being affected by surface tension. Therefore, bone dehydrated using critical point drying can retain or increase at least some surface structure and thus increase surface area.

[0159] In some implementations, carbon dioxide is used for critical point drying. However, other media can be used, such as Freon, which contains Freon 13 (chlorotrifluoromethane). Typically, fluids suitable for supercritical drying include carbon dioxide (critical point at 304.25 K at 7.39 MPa or 31.1 °C or 31.2 °C and 73.8 bar at 1072 psi) and Freon (about 300 K at 3.5–4 MPa or 25–30 °C at 500–600 psi). Nitrous oxide has similar physical behavior to carbon dioxide, but is a potent oxidant in its supercritical state. Supercritical water is also a powerful oxidant, partly because its critical point occurs at such high temperatures (374 °C) and pressures (3212 psi / 647 K and 22.064 MPa).

[0160] In some embodiments, bone may be pretreated to remove water before critical-point drying. Thus, according to one embodiment, the bone matrix is ​​dried using carbon dioxide at (or above) its critical-point state. After demineralization, the bone matrix sample (in water) can be dehydrated to remove residual water content. This dehydration can be achieved, for example, by using a series of gradient ethanol solutions (e.g., deionized water containing 20%, 50%, 70%, 80%, 90%, 95%, and 100% ethanol). In some embodiments, the penetration of tissue with a gradient series of ethanol solutions or alcohols can be automated. For example, pressure and vacuum can be used to accelerate penetration into the tissue.

[0161] kit

[0162] In some embodiments, a means is provided for holding the mesh while it is wound to at least partially encapsulate bone material. The means may be a tray and may be positioned in an upright configuration during placement of the bone material into the mesh. The tray may be a thermoformed tray including a central groove. The tray may or may not be part of a sterile package for the bone implant. The tray may also include protrusions or other features to clamp and / or retain the bone implant in a desired spatial arrangement. Suitable trays for filling caps (e.g., mesh) with bone material are described in U.S. Patent Publication 20180311049 (US Serial No. 15 / 581817, filed April 28, 2017) by Shimko et al. and U.S. Patent Publication 20190021862 (US Serial No. 15 / 656112, filed July 21, 2017) by Kalpakci et al. The entire disclosure of these applications is incorporated herein by reference.

[0163] In several aspects, a kit is provided comprising a bone implant 10 as described herein, the bone implant including a cover 18, which in some aspects may be a mesh 32 configured to be wound to a certain diameter to at least partially enclose bone material 12. The kit may also include at least one of the following: a plurality of size-adjusting rings 44, or a plurality of size-adjusting cylinders 46, or one or more funnels 48 having different diameters, or a funnel 50 having a variable diameter. The plurality of rings or the plurality of size-adjusting cylinders are configured to engage the bone implant to adjust the implant to a desired diameter. One or more funnels including the variable diameter funnel are configured to load the cover 18 with a certain amount of bone material. In some embodiments, the kit includes a separate closure member 24, such as a bone suture. In various embodiments, as described above, the closure member may be one or more strands 42 attached to the mesh 32.

[0164] In some implementations, the mesh can be provided in a wound configuration, and a size-adjusting cylinder 46 can be used to fill the wound mesh. In this way, a predetermined amount of bone material can be added to one or more size-adjusting cylinders to load the desired amount of bone material into the mesh. This can also be achieved using a variable diameter funnel.

[0165] The kit may also include bone materials, such as demineralized bone matrix, allogeneic grafts, xenografts, ceramics, or mixtures thereof. In several aspects, the kit may include, for example... Figure 11 The tray shown is 70.

[0166] In some embodiments, the kit may also include a desiccant to prevent hydrolytic degradation during storage. Useful desiccants for the kits described in this application include, but are not limited to, bags encapsulating silica gel, clay, activated carbon, calcium sulfate, calcium chloride, and molecular sieves (e.g., zeolites).

[0167] In other embodiments, a kit for manufacturing bone implants is provided, wherein the kit includes: a cover comprising a main portion and a closure portion adjacent to the main portion, the closure portion being configured to hold the cover in a coiled configuration to a predetermined diameter to at least partially encapsulate bone material; and an adhesive. In some embodiments, the cover provided in the kit is prepared by 3D printing.

[0168] The kit can be used with bone implants designed for minimally invasive midline lumbar fusion, posterior cervical fusion, and oral and maxillofacial reconstruction surgeries. It can also be used with bone implants for healing vertebral compression fractures, interbody fusion, additional minimally invasive surgeries, posterolateral fusion, correction of scoliosis in adults or children, treatment of long bone defects, osteochondral defects, ridge enlargement (teeth / craniofacial, e.g., patients with missing teeth), sublaminal trauma, tibial plateau defects, filling of bone cysts, wound healing, peritracheal healing, and shaping (cosmetic / plastic / reconstructive surgery).

[0169] The tray may be made of metal, thermoformed material or polymer, such as polyurethane, polyurea, polyether (amide), PEBA, thermoplastic elastomers, copolyesters and styrene-based thermoplastic elastomers, steel, aluminum, stainless steel, titanium, nickel-titanium, metal alloys with high non-ferrous metal content and low iron content, carbon fiber, glass fiber, plastics, ceramics or combinations thereof.

[0170] When the tray is made of thermoforming material, the thermoforming material can be acrylonitrile butadiene styrene (ABS), polymethyl methacrylate (PMMA), or acrylic acid. High-density polyethylene (HDPE), high-impact polystyrene (HIPS), KYDEXTM (PMMA / PVC blend), polycarbonate (PC), polyetherimide (PEI or Polyethylene terephthalate (PETG), polypropylene (PP), polyvinyl chloride (PVC), and thermoplastic polyolefin (TPO).

[0171] The tray can also be made of shape-memory polymers, including but not limited to polyethers, polyacrylates, polyamides, polysiloxanes, polyurethanes, polyetheramides, polyurethane / urea, polyether esters, polynorbornene, crosslinked polymers (e.g., crosslinked polyethylene and crosslinked poly(cyclooctene)), inorganic-organic hybrid polymers, and copolymers such as urethane / butadiene copolymers and styrene-butadiene copolymers. Shape-memory alloys include, but are not limited to, TiNi, CuZnAl, and FeNiAl alloys.

[0172] In some embodiments, the tray may include visual markings, such as, for example, markings that enable a user to measure a defined volume of material placed into the net. In some embodiments, the tray may include length and / or volume markings to aid in filling the net.

[0173] In various embodiments, the kit, along with the bone implant and tray, may include additional components such as scrapers, mixing bowls, wiping agents, needles, measuring devices, and syringes. The kit may include a mesh in the first compartment. The second compartment may include vials containing bone material, diluent, and any other instruments required for local implant delivery. The third compartment may include a tray for filling the bone implant. The fourth compartment may include gloves, drapes, wound dressings, and other surgical supplies for maintaining sterility during the implantation process, as well as an instruction booklet that may include diagrams showing how to implant the bone implant. The fifth compartment may include additional needles, measuring devices, fasteners, and / or sutures. Each tool may be individually packaged in a radiation-sterilized plastic pouch. The sixth compartment may contain agents for radiographic imaging. The kit cap may contain instructions for the implantation procedure, and a transparent plastic cap may be placed on top of the compartments to maintain sterility.

[0174] How to use

[0175] A method is provided for implanting a bone implant at a surgical site under the skin of a patient. The method includes: providing a bone implant 10, the bone implant including a cover 18 configured to be wound to a diameter D to enclose bone material 12 at least within the cover; enclosing the bone material within the cover by adapting the cover to a wound configuration; and placing the bone implant at the surgical site, thereby implanting the bone implant at the surgical site. The bone implant implanted by this method can be, for example... Figures 1 to 3 , Figure 4A , Figure 4B , Figure 5A , Figure 5B , Figure 6 and Figures 7A to 7E The bone implant 10 is shown. Implantation sites correspond to minimally invasive midline lumbar fusion, posterior cervical fusion, and oral and maxillofacial reconstruction surgeries. In many cases, the bone material can be fully demineralized bone fibers and superficially demineralized bone fragments. Implantation sites may also correspond to healing vertebral compression fractures, intervertebral fusion, other minimally invasive surgeries, posterolateral fusion, correction of scoliosis in adults or children, treatment of long bone defects, osteochondral defects, ridge enlargement (teeth / craniofacial, e.g., patients with missing teeth), sublaminal trauma, tibial plateau defects, filling of bone cysts, wound healing, peri-traumatic procedures, and shaping (cosmetic / plastic / reconstructive surgery), etc.

[0176] This method can also be used for surgical treatments in which the patient is in a prone or supine position, and / or with various surgical approaches to the spine and other body areas, including anterior, dorsal, midline dorsal, lateral, and / or anterior approaches. This method can also be used in conjunction with surgeries for the treatment of the lumbar, cervical, thoracic, sacral, and pelvic regions of the spine. The method can also be used on animals, bone models, and other inanimate substrates, for example, for training, testing, and demonstration.

[0177] In some implementations, the ends of the bone implant can be manually sealed by the user, such as... Figure 2 As shown, the user seals the wrapped cover at either end using adhesive 26, 28 or surgical sutures. Alternatively, the net can be wound by the user to encapsulate or partially encapsulate the bone material into the bone implant.

[0178] In some implementations, bone implants can be used for healing vertebral compression fractures, intervertebral fusion, minimally invasive surgery, posterolateral fusion, adult or pediatric scoliosis correction, treatment of long bone defects, osteochondral defects, ridge augmentation (dental / craniofacial, e.g., patients with missing teeth), under traumatic plates, tibial plateau defects, filling bone cysts, wound healing, peri-traumatic procedures, and orthopedic (cosmetic / shaping / reconstructive surgery). Bone implants can be used in minimally invasive procedures via placement through small incisions or other means. Size and shape can be designed to limit delivery conditions.

[0179] Generally, bone implants can be applied to pre-existing defects, formed channels, or modified defects. Thus, for example, a channel can be formed in the bone, or a pre-existing defect can be cut to form a channel for receiving the bone implant. The bone implant can be configured to match a channel or defect. In some embodiments, the configuration of the bone implant can be selected to match a channel. In other embodiments, a channel can be created or the defect can be extended or modified to reflect the configuration of the bone implant. The bone implant can be placed in the defect or channel and optionally coupled using an attachment mechanism.

[0180] In some embodiments, the bone implant of this application may be provided in a dry form of carrier-free bone material (e.g., DBM). Alternatively, the bone material may be hydrated at the point of care with blood, saline, water, glucose, etc., to form a wet material before, during, or after encapsulating the bone material in a covering and implanting it.

[0181] Although the invention has been described with reference to embodiments, those skilled in the art will recognize that changes in form and detail may be made without departing from the spirit and scope of the invention.

Claims

1. A bone implant for encapsulating a bone material, the bone implant comprising a covering comprising a body portion and a closure portion adjacent to the body portion, the closure portion configured to hold the covering in a coiled configuration to a predetermined diameter to at least partially encapsulate the bone material, wherein the body portion comprises a wire having a narrower regular pattern and the closure portion comprises a wire having a wider regular pattern relative to the body portion to at least partially encapsulate the bone material.

2. The bone implant of claim 1, wherein the covering is biodegradable and comprises a mesh.

3. The bone implant of claim 1, wherein the closure portion is (i) more flexible or (ii) more deformable than the body portion.

4. The bone implant of claim 1, wherein the closure portion holds the covering in a coiled configuration without reducing the porosity of the body portion.

5. The bone implant of claim 1, wherein the covering comprises a biodegradable mesh having shape memory to allow positioning from a planar configuration to a coiled configuration to at least partially encapsulate the bone material.

6. The bone implant of claim 2, wherein the mesh comprises at least one of poly(lactide-co-glycolide) (PLGA), poly-lactide (PLA), poly-glycolide (PGA), D-lactide, D,L-lactide, L-lactide, D,L-lactide-co-epsilon-caprolactone, L-lactide-co-epsilon-caprolactone, D,L-lactide-co-glycolide-co-epsilon-caprolactone, poly(D,L-lactide-co-caprolactone), poly(L-lactide-co-caprolactone), poly(D-lactide-co-caprolactone), poly(D,L-lactide), poly(D-lactide), poly(L-lactide), poly(ester amide), hydroxyapatite, calcium phosphate, or ceramic.

7. The bone implant of claim 2, wherein the bone material is completely encapsulated by the mesh, and the mesh is porous to allow cell influx and efflux.

8. The bone implant of claim 2, wherein the mesh further comprises a polymeric coating, the coating comprising a bioactive agent.

9. The bone implant of claim 8, wherein the bioactive agent comprises an osteogenic or chondrogenic protein or peptide, demineralized bone matrix powder, a growth factor, an antibiotic, a drug, or a combination thereof.

10. The bone implant of claim 2, wherein (i) the mesh comprises an inner portion and an outer portion, all or a portion of the inner portion and / or the outer portion comprising an adhesive material disposed thereon; or (ii) the mesh comprises an inner portion and an outer portion, a portion of the inner portion and / or the outer portion having a mating surface configured to hold the mesh in the coiled configuration.

11. The bone implant of claim 10, wherein a first mating surface comprises a protrusion or hook and a second mating surface comprises a mating void for holding the mesh in the coiled configuration.

12. The bone implant of claim 10, wherein (i) the adhesive material is water activated; (ii) the adhesive material is applied at the time of use; (iii) the adhesive material comprises a volatile solvent that, upon evaporation, causes the mesh to become tacky to provide self-adhesion.

13. The bone implant of claim 10, wherein the interior or the exterior of the mesh has a plurality of spaced apart markers to assist in sizing the covering for implantation.

14. A kit for manufacturing a bone implant, the kit comprising: A covering comprising a body portion and a closure portion adjacent to the body portion, the closure portion configured to hold the covering in a coiled configuration to a predetermined diameter to at least partially encapsulate bone material, wherein the body portion comprises a wire having a narrower regular pattern and the closure portion comprises a wire having a wider regular pattern relative to the body portion to at least partially encapsulate bone material; and a package for containing the covering.

15. The kit of claim 14, further comprising a bone material comprising demineralized bone matrix, allograft, xenograft, ceramic, or a combination thereof.

16. The kit of claim 15, further comprising a tray for holding a mesh to facilitate positioning of the bone material into the coiled mesh; and an adhesive.

17. The kit of claim 14, wherein the covering is prepared by 3D printing.

18. Use of a covering encapsulating bone material in the preparation of a bone implant for implantation at a surgical site, the covering comprising a body portion and a closure portion adjacent to the body portion, the closure portion configured to hold the covering in a coiled configuration to a predetermined diameter to at least partially encapsulate the bone material, wherein the body portion comprises a wire having a narrower regular pattern and the closure portion comprises a wire having a wider regular pattern relative to the body portion to at least partially encapsulate bone material; the covering adapted in the coiled configuration to encapsulate the bone material in the covering.

19. The use of claim 18, wherein the bone material is demineralized bone matrix, allograft, xenograft, ceramic, or a combination thereof.

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